Many antibiotics that were once effective including penicillin, tetracycline, and fluoroquinolones are no longer recommended because of high rates of resistance. Resistance to cefixime has reached a level such that it is no longer recommended as a first-line agent in the United States, and if it is used a person should be tested again after a week to determine whether the infection still persists. Cases of resistance to ceftriaxone have been reported but are still rare, though public health officials are concerned that an emerging pattern of resistance may predict a global epidemic. The UK's Health Protection Agency reported that 2011 saw a slight drop in gonorrhea antibiotic resistance, the first in 5 years.

Treatment is based on the prescription and use of the proper antibiotics depending on the strain of the ureaplasma.

Because of its multi-causative nature, initial treatment strategies involve using a broad range antibiotic that is effective against chlamydia (such as doxycycline). It is imperative that both the patient and any sexual contacts be treated. Women infected with the organisms that cause NGU may develop pelvic inflammatory disease. If symptoms persist, follow-up with a urologist may be necessary to identify the cause.

According to a study, tinidazole used with doxycycline or azithromycin may cure NGU better than when doxycycline or azithromycin is used alone.

If left untreated, complications include epididymitis and infertility. Consistent and correct use of latex condoms during sexual activity greatly reduces the likelihood of infection.

As with most sexually transmitted diseases, the risk of infection can be reduced significantly by the correct use of condoms and can be removed almost entirely by limiting sexual activities to a mutually monogamous relationship with an uninfected person.

Those previously infected are encouraged to return for follow up care to make sure that the infection has been eliminated. In addition to the use of phone contact, the use of email and text messaging have been found to improve the re-testing for infection.

"C. trachomatis" infection can be effectively cured with antibiotics. Guidelines recommend azithromycin, doxycycline, erythromycin, levofloxacin or ofloxacin. Agents recommended during pregnancy include erythromycin or amoxicillin.

An option for treating sexual partners of those with chlamydia or gonorrhea include patient-delivered partner therapy (PDT or PDPT), which is the practice of treating the sex partners of index cases by providing prescriptions or medications to the patient to take to his/her partner without the health care provider first examining the partner.

Following treatment people should be tested again after three months to check for reinfection.

Vulvovaginitis in children may be "nonspecific", or caused by irritation with no known infectious cause, or infectious, caused by a pathogenic organism. Nonspecific vulvovaginitis may be triggered by fecal contamination, sexual abuse, chronic diseases, foreign bodies, nonestrogenized epithelium, chemical irritants, eczema, seborrhea, or immunodeficiency. It is treated with topical steroids; antibiotics may be given in cases where itching has resulted in a secondary infection.

Infectious vulvovaginitis can be caused by group A beta-hemolytic "Streptococcus" (7-20% of cases), "Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, Shigella, Yersinia", or common STI organisms ("Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis", herpes simplex virus, and human papillomavirus)"." Symptoms and treatment of infectious vulvovaginitis vary depending on the organism causing it. "Shigella" infections of the reproductive tract usually coexist with infectious of the gastrointestinal tract and cause mucous, purulent discharge. They are treated with trimethoprim-sulfamethoxazole. "Streptococcus" infections cause similar symptoms to nonspecific vulvovaginitis and are treated with amoxicillin. STI-associated vulvovaginitis may be caused by sexual abuse or vertical transmission, and are treated and diagnosed like adult infections.

Treatment can include topical steroids to diminish the inflammation. Antibiotics to diminish the proportion of aerobic bacteria is still a matter of debate. The use of local antibiotics, preferably local non-absorbed and broad spectrum, covering enteric gram-positive and gram-negative aerobes, can be an option. In some cases, systemic antibiotics can be helpful, such as amoxicillin/clavulanate or moxifloxacin. Vaginal rinsing with povidone iodine can provide relief of symptoms but does not provide long-term reduction of bacterial loads. Dequalinium chloride can also be an option for treatment.

Some steps suggested to lower the risk include: not douching, avoiding sex, or limiting the number of sex partners.

One review concluded that probiotics may help prevent re-occurrence. Another review found that while there is tentative evidence it is not strong enough to recommend their use for this purpose.

Early evidence suggested that antibiotic treatment of male partners could re-establish the normal microbiota of the male urogenital tract and prevent the recurrence of infection. However, a 2016 Cochrane review found high-quality evidence that treating the sexual partners of women with bacterial vaginosis had no effect on symptoms, clinical outcomes, or recurrence in the affected women. It also found that such treatment may lead treated sexual partners to report increased adverse events.

A 2009 Cochrane review found tentative but insufficient evidence for probiotics as a treatment for BV. A 2014 review reached the same conclusion. A 2013 review found some evidence supporting the use of probiotics during pregnancy. The preferred probiotics for BV are those containing high doses of lactobacilli (around 10 ) given in the vagina. Intravaginal administration is preferred to taking them by mouth. Prolonged repetitive courses of treatment appear to be more promising than short courses.

For sexually active women who are not pregnant, screening is recommended in those under 25 and others at risk of infection. Risk factors include a history of chlamydial or other sexually transmitted infection, new or multiple sexual partners, and inconsistent condom use. For pregnant women, guidelines vary: screening women with age or other risk factors is recommended by the U.S. Preventive Services Task Force (USPSTF) (which recommends screening women under 25) and the American Academy of Family Physicians (which recommends screening women aged 25 or younger). The American College of Obstetricians and Gynecologists recommends screening all at risk, while the Centers for Disease Control and Prevention recommend universal screening of pregnant women. The USPSTF acknowledges that in some communities there may be other risk factors for infection, such as ethnicity. Evidence-based recommendations for screening initiation, intervals and termination are currently not possible. For men, the USPSTF concludes evidence is currently insufficient to determine if regular screening of men for chlamydia is beneficial. They recommend regular screening of men who are at increased risk for HIV or syphilis infection.

In the United Kingdom the National Health Service (NHS) aims to:

1. Prevent and control chlamydia infection through early detection and treatment of asymptomatic infection;

2. Reduce onward transmission to sexual partners;

3. Prevent the consequences of untreated infection;

4. Test at least 25 percent of the sexually active under 25 population annually.

5. Retest after treatment.

In both the acute and chronic forms, antibiotics are used if an infection is suspected. The treatment of choice is often azithromycin and cefixime to cover both gonorrhoeae and chlamydia. Fluoroquinolones are no longer recommended due to widespread resistance of gonorrhoeae to this class. Doxycycline may be used as an alternative to azithromycin. In chronic epididymitis, a four- to six-week course of antibiotics may be prescribed to ensure the complete eradication of any possible bacterial cause, especially the various chlamydiae.

For cases caused by enteric organisms (such as "E. coli"), ofloxacin or levofloxacin are recommended.

In children, fluoroquinolones and doxycycline are best avoided. Since bacteria that cause urinary tract infections are often the cause of epididymitis in children, co-trimoxazole or suited penicillins (for example, cephalexin) can be used.

Household remedies such as elevation of the scrotum and cold compresses applied regularly to the scrotum may relieve the pain in acute cases. Painkillers or anti-inflammatory drugs are often used for treatment of both chronic and acute forms. Hospitalisation is indicated for severe cases, and check-ups can ensure the infection has cleared up. Surgical removal of the epididymis is rarely necessary, causes sterility, and only gives relief from pain in approximately 50% of cases. However, in acute suppurating epididymitis (acute epididymitis with a discharge of pus), a epididymotomy may be recommended; in refractory cases, a full epididymectomy may be required. In cases with unrelenting testicular pain, removal of the entire testicle—orchiectomy—may also be warranted.

It is generally believed that most cases of chronic epididymitis will eventually "burn out" of patient's system if left untreated, though this might take years or even decades. However, some prostate-related medications have proven effective in treating chronic epididymitis, including doxazosin.

The most common bacterial cause of NGU is "Chlamydia trachomatis", but it can also be caused by "Ureaplasma urealyticum", "Haemophilus vaginalis", "Mycoplasma genitalium", Mycoplasma hominis, Gardnerella vaginalis, Acinetobacter lwoffi, Ac.calcoclaceticus and "E.coli".

A variety of drugs may be prescribed based on the cause of the patient's urethritis. Some examples of medications based on causes include: azithromycin, doxycycline, erythromycin, levofloxacin, metronidazole, ofloxacin, or tinidazole.

Proper perineal hygiene should be stressed. This includes avoiding use of vaginal deodorant sprays and proper wiping after urination and bowel movements. Intercourse should be avoided until symptoms subside.

Risk of some causes of urethritis can be lessened by avoiding unprotected sexual activity, chemicals that could irritate the urethra; this could include detergents or lotions as well as spermicides or contraceptives, and irritation caused by manual manipulation of the urethra.

Treatment involves antibiotics and may involve drainage of the buboes or abscesses by needle aspiration or incision. Further supportive measure may need to be taken: dilatation of the rectal stricture, repair of rectovaginal fistulae, or colostomy for rectal obstruction.

Common antibiotic treatments include: tetracycline (doxycycline) (all tetracyclines, including doxycycline, are contraindicated during pregnancy and in children due to effects on bone development and tooth discoloration), and erythromycin. Azithromycin is also a drug of choice in LGV.

As with all STIs, sex partners of patients who have LGV should be examined and tested for urethral or cervical chlamydial infection. After a positive culture for chlamydia, clinical suspicion should be confirmed with testing to distinguish serotype. Antibiotic treatment should be started if they had sexual contact with the patient during the 30 days preceding onset of symptoms in the patient. Patients with a sexually transmitted disease should be tested for other STDs due to high rates of comorbid infections. Antibiotics are not without risks and prophylaxtic broad antibiotic coverage is not recommended.

Cervicitis can be caused by any of a number of infections, of which the most common are chlamydia and gonorrhea, with chlamydia accounting for approximately 40% of cases. As many half of pregnant women are asymptomatic with a gonorrhea infection of the cervix. "Trichomonas vaginalis" and herpes simplex are less common causes of cervicitis. There is a consistent association of M. genitalium infection and female reproductive tract syndromes. M. genitalium infection is significantly associated with increased risk of cervicitis.

Cervices is inflammation of the uterine cervix. Cervicitis in women has many features in common with urethritis in men and many cases are caused by sexually transmitted infections. Death may occur. Non-infectious causes of cervicitis can include intrauterine devices, contraceptive diaphragms, and allergic reactions to spermicides or latex condoms.

The condition is often confused with vaginismus which is a much simpler condition and easily rectified with simple exercises.

Regular testing for sexually transmitted infections is encouraged for prevention. The risk of contracting pelvic inflammatory disease can be reduced by the following:

- Using barrier methods such as condoms; see human sexual behavior for other listings.

- Seeking medical attention if you are experiencing symptoms of PID.

- Using hormonal combined contraceptive pills also helps in reducing the chances of PID by thickening the cervical mucosal plug & hence preventing the ascent of causative organisms from the lower genital tract.

- Seeking medical attention after learning that a current or former sex partner has, or might have had a sexually transmitted infection.

- Getting a STI history from your current partner and strongly encouraging they be tested and treated before intercourse.

- Diligence in avoiding vaginal activity, particularly intercourse, after the end of a pregnancy (delivery, miscarriage, or abortion) or certain gynecological procedures, to ensure that the cervix closes.

- Reducing the number of sexual partners.

- Sexual monogamy.

- Abstinence

If contact dermatitis is suspected, soaps and other external irritants should be discontinued and a latex allergy should be investigated.

The treatment depends on identification of the cause. Irritants in the environment should be removed. Antibiotics and antifungals can be used to treat the infection, but good hygiene such as keeping the area dry is essential to stop recurrence, however excessive washing with soap can cause contact dermatitis.

If infection is sexually transmitted, sexual partners should be notified and treated.

Posthitis and balanitis (inflammation of the glans penis) usually occur together as balanoposthitis. Circumcision prevents balanoposthitis though balanitis can still occur separately.

Though urinary tract infections in men are rare, bacterial infection is the most common cause of acute epididymitis. The bacteria in the urethra back-track through the urinary and reproductive structures to the epididymis. In rare circumstances, the infection reaches the epididymis via the bloodstream.

In sexually active men, "Chlamydia trachomatis" is responsible for two-thirds of acute cases, followed by "Neisseria gonorrhoeae" and "E. coli" (or other bacteria that cause urinary tract infection). Particularly among men over age 35 in whom the cause is "E. coli", epididymitis is commonly due to urinary tract obstruction. Less common microbes include "Ureaplasma", Mycobacterium, and "cytomegalovirus", or "Cryptococcus" in patients with HIV infection. "E. coli" is more common in boys before puberty, the elderly, and men who have sex with men. In the majority of cases in which bacteria are the cause, only one side of the scrotum or the other is the locus of pain.

Non-infectious causes are also possible. Reflux of sterile urine (urine without bacteria) through the ejaculatory ducts may cause inflammation with obstruction. In children, it may be a response following an infection with enterovirus, adenovirus or "Mycoplasma pneumoniae". Rare non-infectious causes of chronic epididymitis include sarcoidosis (more prevalent in black men) and Behçet's disease.

Any form of epididymitis can be caused by genito-urinary surgery, including prostatectomy and urinary catheterization. Congestive epididymitis is a long-term complication of vasectomy. Chemical epididymitis may also result from drugs such as amiodarone.

Over one million cases of acute salpingitis are reported every year in the US, but the number of incidents is probably larger, due to incomplete and untimely reporting methods and that many cases are reported first when the illness has gone so far that it has developed chronic complications. For women age 16–25, salpingitis is the most common serious infection. It affects approximately 11% of females of reproductive age.

Salpingitis has a higher incidence among members of lower socioeconomic classes. However, this is thought of being an effect of earlier sex debut, multiple partners, and decreased ability to receive proper health care rather than any independent risk factor for salpingitis.

As an effect of an increased risk due to multiple partners, the prevalence of salpingitis is highest for people age 15–24 years. Decreased awareness of symptoms and less will to use contraceptives are also common in this group, raising the occurrence of salpingitis.

The bacteria most associated with salpingitis are:

- N. gonorrhoeae

- Chlamydia trachomatis

- Mycoplasma

- Staphylococcus

- Streptococcus

However, salpingitis is usually polymicrobial, involving many kinds of organisms. Other examples of organisms involved are:

- Ureaplasma urealyticum

- Anaerobic and aerobic bacteria

Treatment is often started without confirmation of infection because of the serious complications that may result from delayed treatment. Treatment depends on the infectious agent and generally involves the use of antibiotic therapy. If there is no improvement within two to three days, the patient is typically advised to seek further medical attention. Hospitalization sometimes becomes necessary if there are other complications. Treating sexual partners for possible STIs can help in treatment and prevention.

For women with PID of mild to moderate severity, parenteral and oral therapies appear to be effective. It does not matter to their short- or long-term outcome whether antibiotics are administered to them as inpatients or outpatients. Typical regimens include cefoxitin or cefotetan plus doxycycline, and clindamycin plus gentamicin. An alternative parenteral regimen is ampicillin/sulbactam plus doxycycline. Erythromycin-based medications can also be used. Another alternative is to use a parenteral regimen with ceftriaxone or cefoxitin plus doxycycline. Clinical experience guides decisions regarding transition from parenteral to oral therapy, which usually can be initiated within 24–48 hours of clinical improvement.

In most cases where orchitis is caused by epididymitis, treatment is an oral antibiotic such as cefalexin or ciprofloxacin until infection clears up. In both causes non-steroidal anti-inflammatory drugs such as naproxen or ibuprofen are recommended to relieve pain. Sometimes stronger pain medications in the opiate category are called for and are frequently prescribed by experienced emergency room physicians.

Sexually transmitted disease that affect the vagina include:

- Herpes genitalis. The herpes simplex virus (HSV) can infect the vulva, vagina, and cervix, and this may result in small, painful, recurring blisters and ulcers. It is also common for there to be an absence of any noticeable symptoms.

- Gonorrhea

- Chlamydia

- Trichomoniasis

- Human papillomavirus (HPV), which may cause genital warts.

HIV/AIDS can be contracted through the vagina during vaginal intercourse, but it is not associated with any local vaginal or vulval disease.

Because of STIs, health authorities and other health outlets recommend safe sex practices when engaging in sexual activity.