Medical management of VHF patients may require intensive supportive care. Antiviral therapy with intravenous ribavirin may be useful in Bunyaviridae and Arenaviridae infections (specifically Lassa fever, RVF, CCHF, and HFRS due to Old World Hantavirus infection) and can be used only under an experimental protocol as investigational new drug (IND) approved by the U.S. Food and Drug Administration (FDA). Interferon may be effective in Argentine or Bolivian hemorrhagic fevers (also available only as IND).

With the exception of yellow fever vaccine neither vaccines nor experimental vaccines are readily available. Prophylactic (preventive) ribavirin may be effective for some bunyavirus and arenavirus infections (again, available only as IND).

VHF isolation guidelines dictate that all VHF patients (with the exception of dengue patients) should be cared for using strict contact precautions, including hand hygiene, double gloves, gowns, shoe and leg coverings, and faceshield or goggles. Lassa, CCHF, Ebola, and Marburg viruses may be particularly prone to nosocomial (hospital-based) spread. Airborne precautions should be utilized including, at a minimum, a fit-tested, HEPA filter-equipped respirator (such as an N-95 mask), a battery-powered, air-purifying respirator, or a positive pressure supplied air respirator to be worn by personnel coming within 1,8 meter (six feet) of a VHF patient. Multiple patients should be cohorted (sequestered) to a separate building or a ward with an isolated air-handling system. Environmental decontamination is typically accomplished with hypochlorite (e.g. bleach) or phenolic disinfectants.

There are no specific antiviral drugs for dengue; however, maintaining proper fluid balance is important. Treatment depends on the symptoms. Those who are able to drink, are passing urine, have no "warning signs" and are otherwise healthy can be managed at home with daily follow-up and oral rehydration therapy. Those who have other health problems, have "warning signs", or cannot manage regular follow-up should be cared for in hospital. In those with severe dengue care should be provided in an area where there is access to an intensive care unit.

Intravenous hydration, if required, is typically only needed for one or two days. In children with shock due to dengue a rapid dose of 20 mL/kg is reasonable. The rate of fluid administration is then titrated to a urinary output of 0.5–1 mL/kg/h, stable vital signs and normalization of hematocrit. The smallest amount of fluid required to achieve this is recommended.

Invasive medical procedures such as nasogastric intubation, intramuscular injections and arterial punctures are avoided, in view of the bleeding risk. Paracetamol (acetaminophen) is used for fever and discomfort while NSAIDs such as ibuprofen and aspirin are avoided as they might aggravate the risk of bleeding. Blood transfusion is initiated early in people presenting with unstable vital signs in the face of a "decreasing hematocrit", rather than waiting for the hemoglobin concentration to decrease to some predetermined "transfusion trigger" level. Packed red blood cells or whole blood are recommended, while platelets and fresh frozen plasma are usually not. There is not enough evidence to determine if corticosteroids have a positive or negative effect in dengue fever.

During the recovery phase intravenous fluids are discontinued to prevent a state of fluid overload. If fluid overload occurs and vital signs are stable, stopping further fluid may be all that is needed. If a person is outside of the critical phase, a loop diuretic such as furosemide may be used to eliminate excess fluid from the circulation.

As for other flavivirus infections, no cure is known for yellow fever. Hospitalization is advisable and intensive care may be necessary because of rapid deterioration in some cases. Different methods for acute treatment of the disease have been shown not to be very successful; passive immunisation after emergence of symptoms is probably without effect. Ribavirin and other antiviral drugs, as well as treatment with interferons, do not have a positive effect in patients.

A symptomatic treatment includes rehydration and pain relief with drugs such as paracetamol (acetaminophen in the United States). Acetylsalicylic acid (aspirin) should not be given because of its anticoagulant effect, which can be devastating in the case of internal bleeding that can occur with yellow fever.

All persons suspected of Lassa fever infection should be admitted to isolation facilities and their body fluids and excreta properly disposed of.

Early and aggressive treatment using ribavirin was pioneered by Joe McCormick in 1979. After extensive testing, early administration was determined to be critical to success. Additionally, ribavirin is almost twice as effective when given intravenously as when taken by mouth. Ribavirin is a prodrug which appears to interfere with viral replication by inhibiting RNA-dependent nucleic acid synthesis, although the precise mechanism of action is disputed. The drug is relatively inexpensive, but the cost of the drug is still very high for many of those in West African states. Fluid replacement, blood transfusion, and fighting hypotension are usually required. Intravenous interferon therapy has also been used.

When Lassa fever infects pregnant women late in their third trimester, induction of delivery is necessary for the mother to have a good chance of survival. This is because the virus has an affinity for the placenta and other highly vascular tissues. The fetus has only a one in ten chance of survival no matter what course of action is taken; hence, the focus is always on saving the life of the mother. Following delivery, women should receive the same treatment as other Lassa fever patients.

Work on a vaccine is continuing, with multiple approaches showing positive results in animal trials.

Omsk Hemorrhagic Fever could be diagnosed by isolating virus from blood, or by serologic testing using immunosorbent serological assay. OHF rating of fatality is 0.5–3%. There is no specific treatment for OHF so far but one way to help get rid of OHF is by supportive therapy. Supportive therapy helps maintain hydration and helps to provide precautions for patients with bleeding disorders.

Effective antibiotics include penicillin G, ampicillin, amoxicillin and doxycycline. In more severe cases cefotaxime or ceftriaxone should be preferred.

Glucose and salt solution infusions may be administered; dialysis is used in serious cases. Elevations of serum potassium are common and if the potassium level gets too high special measures must be taken. Serum phosphorus levels may likewise increase to unacceptable levels due to kidney failure.

Treatment for hyperphosphatemia consists of treating the underlying disease, dialysis where appropriate, or oral administration of calcium carbonate, but not without first checking the serum calcium levels (these two levels are related). Administration of corticosteroids in gradually reduced doses (e.g., prednisolone) for 7–10 days is recommended by some specialists in cases of severe hemorrhagic effects. Organ-specific care and treatment are essential in cases of kidney, liver, or heart involvement.

No specific treatment for CTF is yet available. The first action is make sure the tick is fully removed from the skin, then acetaminophen and analgesics can be used to help relieve the fever and pain. Aspirin is not recommended for children, as it has been linked to Reye’s syndrome in some viral illnesses. Salicylates should not be used because of thrombocytopenia, and the rare occurrence of bleeding disorders. People who suspect they have been bitten by a tick or are starting to show signs of CTF should contact their physicians immediately.

Oropouche Fever has no cure or specific therapy so treatment is done by relieving the pain of the symptoms through symptomatic treatment. Certain oral analgesic and anti-inflammatory agents can help treat headaches and body pains. In extreme cases of oropouche fever the drug, Ribavirin is recommended to help against the virus. This is called antiviral therapy. Treatments also consist of drinking lots of fluids to prevent dehydration.

Asprin is not a recommended choice of drug because it can reduce blood clotting and may aggravate the hemorrhagic effects and prolong recovery time.

The infection is usually self-limiting and complications are rare. This illness usually lasts for about a week but in extreme cases can be prolonged. Patients usually recover fully with no long term ill effects. There have been no recorded fatalities resulting from oropouche fever.

Preventing Omsk Hemorrhagic Fever consists primarily in avoiding being exposed to tick. Persons engaged in camping, farming, forestry, hunting (especially the Siberian muskrat) are at greater risk and should wear protective clothing or use insect repellent for protection. The same is generally recommended for persons at sheltered locations.

Treatment is similar to hepatitis B, but due to its high lethality, more aggressive therapeutic approaches are recommended in the acute phase. In absence of a specific vaccine against delta virus, the vaccine against HBV must be given soon after birth in risk groups.

Prophylaxis by vaccination, as well as preventive measures like protective clothing, tick control, and mosquito control are advised. The vaccine for KFDV consists of formalin-inactivated KFDV. The vaccine has a 62.4% effectiveness rate for individuals who receive two doses. For individuals who receive an additional dose, the effectiveness increases to 82.9%. Specific treatments are not available.

Ticks should be removed promptly and carefully with tweezers and by applying gentle, steady traction. The tick's body should not be crushed when it is removed and the tweezers should be placed as close to the skin as possible to avoid leaving tick mouthparts in the skin; mouthparts left in the skin can allow secondary infections. Ticks should not be removed with bare hands. Hands should be protected by gloves and/or tissues and thoroughly washed with soap and water after the removal process.

A match or flame should not be used to remove a tick. This method, once thought safe, can cause the tick to regurgitate, expelling any disease it may be carrying into the bite wound.

There is no cure or vaccine for HFRS. Treatment involves supportive therapy including renal dialysis. Treatment with ribavirin in China and Korea, administered within 7 days of onset of fever, resulted in a reduced mortality as well as shortened course of illness.

There is no treatment currently available. The virus generally resolves itself within a five to seven day period. The use of steroids can actually cause a corneal microbial superinfection which then requires antimicrobial therapy to eliminate.

Prevention depends on control of and protection from the bites of the mosquito that transmits it. The World Health Organization recommends an Integrated Vector Control program consisting of five elements:

1. Advocacy, social mobilization and legislation to ensure that public health bodies and communities are strengthened;

2. Collaboration between the health and other sectors (public and private);

3. An integrated approach to disease control to maximize use of resources;

4. Evidence-based decision making to ensure any interventions are targeted appropriately; and

5. Capacity-building to ensure an adequate response to the local situation.

The primary method of controlling "A. aegypti" is by eliminating its habitats. This is done by getting rid of open sources of water, or if this is not possible, by adding insecticides or biological control agents to these areas. Generalized spraying with organophosphate or pyrethroid insecticides, while sometimes done, is not thought to be effective. Reducing open collections of water through environmental modification is the preferred method of control, given the concerns of negative health effects from insecticides and greater logistical difficulties with control agents. People can prevent mosquito bites by wearing clothing that fully covers the skin, using mosquito netting while resting, and/or the application of insect repellent (DEET being the most effective). However, these methods appear not to be sufficiently effective, as the frequency of outbreaks appears to be increasing in some areas, probably due to urbanization increasing the habitat of "A. aegypti". The range of the disease appears to be expanding possibly due to climate change.

Vaccination is recommended for those traveling to affected areas, because non-native people tend to develop more severe illness when infected. Protection begins by the 10th day after vaccine administration in 95% of people, and had been reported to last for at least 10 years. WHO now states that a single dose of vaccination is sufficient to confer lifelong immunity against yellow fever disease." The attenuated live vaccine stem 17D was developed in 1937 by Max Theiler. The World Health Organization (WHO) recommends routine vaccinations for people living in affected areas between the 9th and 12th month after birth.

Up to one in four people experience fever, aches, and local soreness and redness at the site of injection. In rare cases (less than one in 200,000 to 300,000), the vaccination can cause yellow fever vaccine–associated viscerotropic disease, which is fatal in 60% of cases. It is probably due to the genetic morphology of the immune system. Another possible side effect is an infection of the nervous system, which occurs in one in 200,000 to 300,000 cases, causing yellow fever vaccine-associated neurotropic disease, which can lead to meningoencephalitis and is fatal in less than 5% of cases.

The Yellow Fever Initiative, launched by WHO in 2006, vaccinated more than 105 million people in 14 countries in West Africa. No outbreaks were reported during 2015. The campaign was supported by the GAVI Alliance, and governmental organizations in Europe and Africa. According to the WHO, mass vaccination cannot eliminate yellow fever because of the vast number of infected mosquitoes in urban areas of the target countries, but it will significantly reduce the number of people infected.

In March 2017, WHO launched a vaccination campaign in Brazil with 3.5 million doses from an emergency stockpile. In March 2017 the WHO recommended vaccination for travellers to certain parts of Brazil.

There is currently no effective marburgvirus-specific therapy for MVD. Treatment is primarily supportive in nature and includes minimizing invasive procedures, balancing fluids and electrolytes to counter dehydration, administration of anticoagulants early in infection to prevent or control disseminated intravascular coagulation, administration of procoagulants late in infection to control hemorrhaging, maintaining oxygen levels, pain management, and administration of antibiotics or antimycotics to treat secondary infections. Experimentally, recombinant vesicular stomatitis Indiana virus (VSIV) expressing the glycoprotein of MARV has been used successfully in nonhuman primate models as post-exposure prophylaxis. Novel, very promising, experimental therapeutic regimens rely on antisense technology: phosphorodiamidate morpholino oligomers (PMOs) targeting the MARV genome could prevent disease in nonhuman primates. Leading medications from Sarepta and Tekmira both have been successfully used in European humans as well as primates.

Supportive care must be provided to animals that have clinical signs. Subcutaneous or intravenous fluids are given to dehydrated animals, and severely anemic dogs may require a blood transfusion. Treatment for ehrlichiosis involves the use of antibiotics such as tetracycline or doxycycline for a period of at least six to eight weeks; response to the drugs may take one month. Treatment with macrolide antibiotics like clarithromycin and azithromycin is being studied. In addition, steroids may be indicated in severe cases in which the level of platelets is so low that the condition is life-threatening.

Investigational vaccines exist for Argentine hemorrhagic fever and RVF; however, neither is approved by FDA or commonly available in the United States.

The structure of the attachment glycoprotein has been determined by X-ray crystallography and this glycoprotein is likely to be an essential component of any successful vaccine.

Tick control is the most effective method of prevention, but tetracycline at a lower dose can be given daily for 200 days during the tick season in endemic regions.

A vaccine has been conditionally approved for use in animals in the US. It has been shown that knockout of the NSs and NSm nonstructural proteins of this virus produces an effective vaccine in sheep as well.

Doxycycline has been provided once a week as a prophylaxis to minimize infections during outbreaks in endemic regions. However, there is no evidence that chemoprophylaxis is effective in containing outbreaks of leptospirosis, and use of antibiotics increases antibiotics resistance. Pre-exposure prophylaxis may be beneficial for individuals traveling to high-risk areas for a short stay.

Effective rat control and avoidance of urine contaminated water sources are essential preventive measures. Human vaccines are available only in a few countries, such as Cuba and China. Animal vaccines only cover a few strains of the bacteria. Dog vaccines are effective for at least one year.

Treatment is primarily supportive in nature. Early supportive care with rehydration and symptomatic treatment improves survival. Rehydration may be via the oral or by intravenous route. These measures may include management of pain, nausea, fever and anxiety. The World Health Organization recommends avoiding the use of aspirin or ibuprofen for pain due to the bleeding risk associated with use of these medications.

Blood products such as packed red blood cells, platelets or fresh frozen plasma may also be used. Other regulators of coagulation have also been tried including heparin in an effort to prevent disseminated intravascular coagulation and clotting factors to decrease bleeding. Antimalarial medications and antibiotics are often used before the diagnosis is confirmed, though there is no evidence to suggest such treatment helps. A number of experimental treatments are being studied.

If hospital care is not possible, the World Health Organization has guidelines for care at home that have been relatively successful. In such situations, recommendations include using towels soaked in bleach solutions when moving infected people or bodies and applying bleach on stains. It is also recommended that the caregivers wash hands with bleach solutions and cover their mouth and nose with a cloth.

Treatment is mostly supportive. Ribavirin is effective "in vitro" and has been used by mouth during outbreaks, but there is no trial evidence to support its use.

The United States armed forces maintain special stocks of ribavirin to protect personnel deployed to Afghanistan and Iraq from CCHF.