Following active infection, herpes viruses establish a latent infection in sensory and autonomic ganglia of the nervous system. The double-stranded DNA of the virus is incorporated into the cell physiology by infection of the nucleus of a nerve's cell body. HSV latency is static; no virus is produced; and is controlled by a number of viral genes, including latency-associated transcript.

Many HSV-infected people experience recurrence within the first year of infection. Prodrome precedes development of lesions. Prodromal symptoms include tingling (paresthesia), itching, and pain where lumbosacral nerves innervate the skin. Prodrome may occur as long as several days or as short as a few hours before lesions develop. Beginning antiviral treatment when prodrome is experienced can reduce the appearance and duration of lesions in some individuals. During recurrence, fewer lesions are likely to develop and are less painful and heal faster (within 5–10 days without antiviral treatment) than those occurring during the primary infection. Subsequent outbreaks tend to be periodic or episodic, occurring on average four or five times a year when not using antiviral therapy.

The causes of reactivation are uncertain, but several potential triggers have been documented. A 2009 study showed the protein VP16 plays a key role in reactivation of the dormant virus. Changes in the immune system during menstruation may play a role in HSV-1 reactivation. Concurrent infections, such as viral upper respiratory tract infection or other febrile diseases, can cause outbreaks. Reactivation due to other infections is the likely source of the historic terms 'cold sore' and 'fever blister'.

Other identified triggers include local injury to the face, lips, eyes, or mouth; trauma; surgery; radiotherapy; and exposure to wind, ultraviolet light, or sunlight.

The frequency and severity of recurrent outbreaks vary greatly between people. Some individuals' outbreaks can be quite debilitating, with large, painful lesions persisting for several weeks, while others experience only minor itching or burning for a few days. Some evidence indicates genetics play a role in the frequency of cold sore outbreaks. An area of human chromosome 21 that includes six genes has been linked to frequent oral herpes outbreaks. An immunity to the virus is built over time. Most infected individuals experience fewer outbreaks and outbreak symptoms often become less severe. After several years, some people become perpetually asymptomatic and no longer experience outbreaks, though they may still be contagious to others. Immunocompromised individuals may experience longer, more frequent, and more severe episodes. Antiviral medication has been proven to shorten the frequency and duration of outbreaks. Outbreaks may occur at the original site of the infection or in proximity to nerve endings that reach out from the infected ganglia. In the case of a genital infection, sores can appear at the original site of infection or near the base of the spine, the buttocks, or the back of the thighs.

HSV-2-infected individuals are at higher risk for acquiring HIV when practicing unprotected sex with HIV-positive persons, in particular during an outbreak with active lesions.

As with almost all sexually transmitted infections, women are more susceptible to acquiring genital HSV-2 than men. On an annual basis, without the use of antivirals or condoms, the transmission risk of HSV-2 from infected male to female is about 8–11%.

This is believed to be due to the increased exposure of mucosal tissue to potential infection sites. Transmission risk from infected female to male is around 4–5% annually. Suppressive antiviral therapy reduces these risks by 50%. Antivirals also help prevent the development of symptomatic HSV in infection scenarios, meaning the infected partner will be seropositive but symptom-free by about 50%. Condom use also reduces the transmission risk significantly. Condom use is much more effective at preventing male-to-female transmission than "vice versa". Previous HSV-1 infection may reduce the risk for acquisition of HSV-2 infection among women by a factor of three, although the one study that states this has a small sample size of 14 transmissions out of 214 couples.

However, asymptomatic carriers of the HSV-2 virus are still contagious. In many infections, the first symptom people will have of their own infections is the horizontal transmission to a sexual partner or the vertical transmission of neonatal herpes to a newborn at term. Since most asymptomatic individuals are unaware of their infection, they are considered at high risk for spreading HSV.

In October 2011, the anti-HIV drug tenofovir, when used topically in a microbicidal vaginal gel, was reported to reduce herpes virus sexual transmission by 51%.

The majority of cases (85%) occur during birth when the baby comes in contact with infected genital secretions in the birth canal, most common with mothers that have newly been exposed to the virus (mothers that had the virus before pregnancy have a lower risk of transmission), an estimated 5% are infected in utero, and approximately 10% of cases are acquired postnatally. Detection and prevention is difficult because transmission is asymptomatic in 60% - 98% of cases.

Neonatal HSV rates in the U.S. are estimated to be between 1 in 3,000 and 1 in 20,000 live births. Approximately 22% of pregnant women in the U.S. have had previous exposure to HSV-2, and an additional 2% acquire the virus during pregnancy, mirroring the HSV-2 infection rate in the general population. The risk of transmission to the newborn is 30-57% in cases where the mother acquired a primary infection in the third trimester of pregnancy. Risk of transmission by a mother with existing antibodies for both HSV-1 and HSV-2 has a much lower (1-3%) transmission rate. This in part is due to the transfer of significant titer of protective maternal antibodies to the fetus from about the seventh month of pregnancy. However, shedding of HSV-1 from both primary genital infection and reactivations is associated with higher transmission from mother to infant.

HSV-1 neonatal herpes is extremely rare in developing countries because development of HSV-1 specific antibodies usually occurs in childhood or adolescence, precluding a later genital HSV-1 infection. HSV-2 infections are much more common in these countries. In industrialized nations, the adolescent HSV-1 seroprevalance has been dropping steadily for the last 5 decades. The resulting increase in the number of young women becoming sexually active while HSV-1 seronegative has contributed to increased HSV-1 genital herpes rates, and as a result, increased HSV-1 neonatal herpes in developed nations. A recent three-year study in Canada (2000–2003) revealed a neonatal HSV incidence of 5.9 per 100,000 live births and a case fatality rate of 15.5%. HSV-1 was the cause of 62.5% of cases of neonatal herpes of known type, and 98.3% of transmission was asymptomatic. Asymptomatic genital HSV-1 has been shown to be more infectious to the neonate, and is more likely to produce neonatal herpes, than HSV-2, However, with prompt application of antiviral therapy, the prognosis of neonatal HSV-1 infection is better than that for HSV-2.

Varicella zoster virus (VZV) has a high level of infectivity and has a worldwide prevalence. Shingles is a re-activation of latent VZV infection: zoster can only occur in someone who has previously had chickenpox (varicella).

Shingles has no relationship to season and does not occur in epidemics. There is, however, a strong relationship with increasing age. The incidence rate of shingles ranges from 1.2 to 3.4 per 1,000 person‐years among younger healthy individuals, increasing to 3.9–11.8 per 1,000 person‐years among those older than 65 years, and incidence rates worldwide are similar.

This relationship with age has been demonstrated in many countries, and is attributed to the fact that cellular immunity declines as people grow older.

Another important risk factor is immunosuppression. Other risk factors include psychological stress. According to a study in North Carolina, "black subjects were significantly less likely to develop zoster than were white subjects." It is unclear whether the risk is different by gender. Other potential risk factors include mechanical trauma and exposure to immunotoxins.

There is no strong evidence for a genetic link or a link to family history. A 2008 study showed that people with close relatives who had had shingles were twice as likely to develop it themselves, but a 2010 study found no such link.

Adults with latent VZV infection who are exposed intermittently to children with chickenpox receive an immune boost. This periodic boost to the immune system helps to prevent shingles in older adults. When routine chickenpox vaccination was introduced in the United States, there was concern that, because older adults would no longer receive this natural periodic boost, there would be an increase in the incidence of shingles.

Multiple studies and surveillance data, at least when viewed superficially, demonstrate no consistent trends in incidence in the U.S. since the chickenpox vaccination program began in 1995. However, upon closer inspection, the two studies that showed no increase in shingles incidence were conducted among populations where varicella vaccination was not as yet widespread in the community. A later study by Patel "et al." concluded that since the introduction of the chickenpox vaccine, hospitalization costs for complications of shingles increased by more than $700 million annually for those over age 60. Another study by Yih "et al". reported that as varicella vaccine coverage in children increased, the incidence of varicella decreased, and the occurrence of shingles among adults increased by 90%. The results of a further study by Yawn "et al". showed a 28% increase in shingles incidence from 1996 to 2001. It is likely that incidence rate will change in the future, due to the aging of the population, changes in therapy for malignant and autoimmune diseases, and changes in chickenpox vaccination rates; a wide adoption of zoster vaccination could dramatically reduce the incidence rate.

In one study, it was estimated that 26% of those who contract shingles eventually present complications. Postherpetic neuralgia arises in approximately 20% of people with shingles. A study of 1994 California data found hospitalization rates of 2.1 per 100,000 person-years, rising to 9.3 per 100,000 person-years for ages 60 and up. An earlier Connecticut study found a higher hospitalization rate; the difference may be due to the prevalence of HIV in the earlier study, or to the introduction of antivirals in California before 1994.

The rash and pain usually subside within three to five weeks, but about one in five people develop a painful condition called postherpetic neuralgia, which is often difficult to manage. In some people, shingles can reactivate presenting as "zoster sine herpete": pain radiating along the path of a single spinal nerve (a "dermatomal distribution"), but without an accompanying rash. This condition may involve complications that affect several levels of the nervous system and cause many cranial neuropathies, polyneuritis, myelitis, or aseptic meningitis. Other serious effects that may occur in some cases include partial facial paralysis (usually temporary), ear damage, or encephalitis. During pregnancy, first infections with VZV, causing chickenpox, may lead to infection of the fetus and complications in the newborn, but chronic infection or reactivation in shingles are not associated with fetal infection.

There is a slightly increased risk of developing cancer after a shingles infection. However, the mechanism is unclear and mortality from cancer did not appear to increase as a direct result of the presence of the virus. Instead, the increased risk may result from the immune suppression that allows the reactivation of the virus.

Although shingles typically resolves within 3–5 weeks, certain complications may arise:

- Secondary bacterial infection

- Motor involvement, including weakness especially in "motor herpes zoster"

- Eye involvement: trigeminal nerve involvement (as seen in herpes ophthalmicus) should be treated early and aggressively as it may lead to blindness. Involvement of the tip of the nose in the zoster rash is a strong predictor of herpes ophthalmicus.

- Postherpetic neuralgia, a condition of chronic pain following shingles

About 16 percent of Americans between the ages of 14 and 49 are infected with genital herpes, making it one of the most common sexually transmitted diseases. More than 80% of those infected are unaware of their infection. Annually, 776,000 people in the United States get new herpes infections.

Tests for herpes are not routinely included among STD screenings. Performers in the pornography industry are screened for HIV, chlamydia, and gonorrhea with an optional panel of tests for hepatitis B, hepatitis C and syphilis, but not herpes. Testing for herpes is controversial since the results are not always accurate or helpful. Most sex workers and performers will contract herpes at some point in their careers whether they use protection or not.

Herpes labialis is common throughout the world. A large survey of young adults on six continents reported that 33% of males and 28% of females had herpes labialis on two or more occasions during the year before the study. The lifetime prevalence in the United States of America is estimated at 20–45% of the adult population. Lifetime prevalence in France was reported by one study as 32% in males and 42% in females. In Germany, the prevalence was reported at 32% in people aged between 35 and 44 years, and 20% in those aged 65–74. In Jordan, another study reported a lifetime prevalence of 26%.

Key measures to prevent outbreaks of the disease are maintaining hygiene standards and using screening to exclude persons with suspicious infections from engaging in contact sports. A skin check performed before practice or competition takes place can identify individuals who should be evaluated, and if necessary treated by a healthcare professional. In certain situations, i.e. participating in wrestling camps, consider placing participants on valacyclovir 1GM daily for the duration of camp. 10-year study has shown 89.5% reduction in outbreaks and probable prevention of contracting the virus. Medication must be started 5 days before participation to ensure proper concentrations exist.

Testing peoples blood, including those who are pregnant, who do not have symptoms for HSV is not recommended. This is due to concerns of greater harm than benefit such as relationship problems in the setting of a high rate of tests that may be falsely positive.

Herpes gladiatorum is only caused by the herpes simplex virus. Shingles, also manifesting as skin rashes with blisters, is caused by a different virus, herpes zoster. Other agents may cause skin infections, for example ringworm is primarily due to the fungal dermatophyte, "T. tonsurans". Impetigo, cellulitis, folliculitis and carbuncles are usually due to "Staphylococcus aureus" or Beta-hemolytic streptococcus bacteria. These less common forms can be potentially more serious. Anti-viral treatments will not have an effect in non-viral cases. Bacterial infections must be treated with antibiotics and fungal infections with anti-fungal medication.

The likelihood of the infection being spread can be reduced through behaviors such as avoiding touching an active outbreak site, washing hands frequently while the outbreak is occurring, not sharing items that come in contact with the mouth, and not coming into close contact with others (by avoiding kissing, oral sex, or contact sports).

Because the onset of an infection is difficult to predict, lasts a short period of time and heals rapidly, it is difficult to conduct research on cold sores. Though famciclovir improves lesion healing time, it is not effective in preventing lesions; valaciclovir and a mixture of acyclovir and hydrocortisone are similarly useful in treating outbreaks but may also help prevent them.

Acyclovir and valacyclovir by mouth are effective in preventing recurrent herpes labialis if taken prior to the onset of any symptoms or exposure to any triggers. Evidence does not support L-lysine.

Herpes simplex virus is commonly found in humans, yet uncommonly results in systemic manifestations. Suppression of HIV with antiretroviral medications, careful monitoring of immunosuppressive medications are important means of prevention. Antiviral prophylaxis such as daily acyclovir in immunocompromised individuals may be considered.

In children the primary source of infection is the orofacial area, and it is commonly inferred that the virus (in this case commonly HSV-1) is transferred by the cutting, chewing or sucking of fingernail or thumbnail.

In adults, it is more common for the primary source to be the genital region, with a corresponding preponderance of HSV-2. It is also seen in adult health care workers such as dentists because of increased exposure to the herpes virus.

Contact sports are also a potential source of infection with herpetic whitlows.

The duration of the visible blistering caused by varicella zoster virus varies in children usually from 4 to 7 days, and the appearance of new blisters begins to subside after the fifth day. Chickenpox infection is milder in young children, and symptomatic treatment, with sodium bicarbonate baths or antihistamine medication may ease itching. It is recommended to keep new infants from birth up to age 6 months away from an infected person for 10 to 21 days because their immune systems are not developed enough to handle the stress it can bring on. Paracetamol (acetaminophen) is widely used to reduce fever. Aspirin, or products containing aspirin, should not be given to children with chickenpox, as it can cause Reye's Syndrome.

In adults, the disease is more severe, though the incidence is much less common. Infection in adults is associated with greater morbidity and mortality due to pneumonia (either direct viral pneumonia or secondary bacterial pneumonia), bronchitis (either viral bronchitis or secondary bacterial bronchitis), hepatitis, and encephalitis. In particular, up to 10% of pregnant women with chickenpox develop pneumonia, the severity of which increases with onset later in gestation. In England and Wales, 75% of deaths due to chickenpox are in adults. Inflammation of the brain, or encephalitis, can occur in immunocompromised individuals, although the risk is higher with herpes zoster. Necrotizing fasciitis is also a rare complication.

Varicella can be lethal to adults with impaired immunity. The number of people in this high-risk group has increased, due to the HIV epidemic and the increased use of immunosuppressive therapies. Varicella is a particular problem in hospitals, when there are patients with immune systems weakened by drugs (e.g., high-dose steroids) or HIV.

Secondary bacterial infection of skin lesions, manifesting as impetigo, cellulitis, and erysipelas, is the most common complication in healthy children. Disseminated primary varicella infection usually seen in the immunocompromised may have high morbidity. Ninety percent of cases of varicella pneumonia occur in the adult population. Rarer complications of disseminated chickenpox include myocarditis, hepatitis, and glomerulonephritis.

Hemorrhagic complications are more common in the immunocompromised or immunosuppressed populations, although healthy children and adults have been affected. Five major clinical syndromes have been described: febrile purpura, malignant chickenpox with purpura, postinfectious purpura, purpura fulminans, and anaphylactoid purpura. These syndromes have variable courses, with febrile purpura being the most benign of the syndromes and having an uncomplicated outcome. In contrast, malignant chickenpox with purpura is a grave clinical condition that has a mortality rate of greater than 70%. The cause of these hemorrhagic chickenpox syndromes is not known.

Although it is a self-limited illness, oral or intravenous antiviral treatments, particularly acyclovir, have been used in the management of immunocompromised or severely infected patients. Topical acyclovir has not been shown to be effective in management of herpetic whitlow. Famciclovir has been demonstrated to effectively treat and prevent recurrent episodes. Lancing or surgically debriding the lesion may make it worse by causing a superinfection or encephalitis.

Antivirals such as acyclovir, famciclovir, or valacyclovir may be used. Intravenous acyclovir is reserved for individuals who cannot swallow due to the pain, individuals with other systemic manifestations of herpes or severely immunocompromised individuals.

Developing countries are more severely affected by TORCH syndrome.

Many viral infections of the central nervous system occur in seasonal peaks or as epidemics, whereas others, such as herpes simplex encephalitis, are sporadic. In endemic areas it is mostly a disease of children, but as the disease spreads to new regions, or nonimmune travelers visit endemic regions, nonimmune adults are also affected.

TORCH syndrome can be prevented by treating an infected pregnant person, thereby preventing the infection from affecting the fetus.

Meningitis is a very common in children. Newborns can develop herpes virus infections through contact with infected secretions in the birth canal. Other viral infections are acquired by breathing air contaminated with virus-containing droplets exhaled by an infected person. Arbovirus infections are acquired from bites by infected insects (called epidemic encephalitis). Viral central nervous system infections in newborns and infants usually begin with fever. The inability of infants to communicate directly makes it difficult to understand their symptoms. Newborns may have no other symptoms and may initially not otherwise appear ill. Infants older than a month or so typically become irritable and fussy and refuse to eat. Vomiting is common. Sometimes the soft spot on top of a newborn's head (fontanelle) bulges, indicating an increase in pressure on the brain. Because irritation of the meninges is worsened by movement, an infant with meningitis may cry more, rather than calm down, when picked up and rocked. Some infants develop a strange, high-pitched cry. Infants with encephalitis often have seizures or other abnormal movements. Infants with severe encephalitis may become lethargic and comatose and then die. To make the diagnosis of meningitis or the diagnosis of encephalitis, doctors do a spinal tap (lumbar puncture) to obtain cerebrospinal fluid (CSF) for laboratory analysis in children.

After a chickenpox infection, the virus remains dormant in the body's nerve tissues. The immune system keeps the virus at bay, but later in life, usually in an adult, it can be reactivated and cause a different form of the viral infection called shingles (also known as herpes zoster).

The United States Advisory Committee on Immunization Practices (ACIP) suggests that every adult over the age of 60 years get the "herpes zoster" vaccine.

Shingles affects one in five adults infected with chickenpox as children, especially those who are immune-suppressed, particularly from cancer, HIV, or other conditions. Stress can bring on shingles as well, although scientists are still researching the connection. Shingles are most commonly found in adults over the age of 60 who were diagnosed with chickenpox when they were under the age of 1.

Herpesviral encephalitis is encephalitis due to herpes simplex virus.

Herpes simplex encephalitis (HSE) is a viral infection of the human central nervous system. It is estimated to affect at least 1 in 500,000 individuals per year and some studies suggest an incidence rate of 5.9 cases per 100,000 live births. The majority of cases of herpes encephalitis are caused by herpes simplex virus-1 (HSV-1), the same virus that causes cold sores. 57% of American adults are infected with HSV-1, which is spread through droplets, casual contact, and sometimes sexual contact, though most infected people never have cold sores. About 10% of cases of herpes encephalitis are due to HSV-2, which is typically spread through sexual contact. About 1 in 3 cases of HSE result from primary HSV-1 infection, predominantly occurring in individuals under the age of 18; 2 in 3 cases occur in seropositive persons, few of whom have history of recurrent orofacial herpes. Approximately 50% of individuals who develop HSE are over 50 years of age.

Herpesviral Encephalitis can be treated with high-dose intravenous acyclovir. Without treatment, HSE results in rapid death in approximately 70% of cases; survivors suffer severe neurological damage. When treated, HSE is still fatal in one-third of cases, and causes serious long-term neurological damage in over half of survivors. Twenty percent of treated patients recover with minor damage. Only a small population of survivors (2.5%) regain completely normal brain function. Indeed, many amnesic cases in the scientific literature have etiologies involving HSE. Earlier treatment (within 48 hours of symptom onset) improves the chances of a good recovery. Rarely, treated individuals can have relapse of infection weeks to months later. There is evidence that aberrant inflammation triggered by herpes simplex can result in granulomatous inflammation in the brain, which responds to steroids. While the herpes virus can be spread, encephalitis itself is not infectious. Other viruses can cause similar symptoms of encephalitis, though usually milder (Herpesvirus 6, varicella zoster virus, Epstein-Barr, cytomegalovirus, coxsackievirus, etc.).

Herpesviral meningitis is meningitis associated with herpes simplex virus (HSV).

HSV-2 is the most common cause of Mollaret's meningitis, a type of recurrent viral meningitis. This condition was first described in 1944 by French neurologist Pierre Mollaret. Recurrences usually last a few days or a few weeks, and resolve without treatment. They may recur weekly or monthly for approximately 5 years following primary infection.