Tetracycline-group antibiotics (doxycycline, tetracycline) are commonly used. Chloramphenicol is an alternative medication recommended under circumstances that render use of tetracycline derivates undesirable, such as severe liver malfunction, kidney deficiency, in children under nine years and in pregnant women. The drug is administered for seven to ten days.

The treatment for bacillary angiomatosis is erythromycin given for three to four months.

African tick bite fever is usually mild, and most patients do not need more than at-home treatment with antibiotics for their illness. However, because so few patients with this infection visit a doctor, the best antibiotic choice, dose and length of treatment are not well known. Typically doctors treat this disease with antibiotics that have been used effectively for the treatment of other diseases caused by bacteria of similar species, such as Rocky Mountain Spotted Fever.

For mild cases, people are usually treated with one of the following:

- doxycycline

- chloramphenicol

- ciprofloxacin

If a person has more severe symptoms, like a high fever or serious headache, the infection can be treated with doxycycline for a longer amount of time. Pregnant women should not use doxycycline or ciprofloxacin as both antibiotics can cause problems in fetuses. Josamycin has been used effectively for treatment of pregnant women with other rickettsial diseases, but it is unclear if it has a role in the treatment of ATBF.

Appropriate antibiotic treatment should be started immediately when there is a suspicion of Rocky Mountain spotted fever on the basis of clinical and epidemiological findings. Treatment should not be delayed until laboratory confirmation is obtained. In fact, failure to respond to a tetracycline argues against a diagnosis of Rocky Mountain spotted fever. Severely ill patients may require longer periods before their fever resolves, especially if they have experienced damage to multiple organ systems. Preventive therapy in healthy patients who have had recent tick bites is not recommended and may, in fact, only delay the onset of disease.

Doxycycline (a tetracycline) (for adults at 100 milligrams every 12 hours, or for children under at 4 mg/kg of body weight per day in two divided doses) is the drug of choice for patients with Rocky Mountain spotted fever, being one of the only instances doxycycline is used in children. Treatment should be continued for at least three days after the fever subsides, and until there is unequivocal evidence of clinical improvement. This will be generally for a minimum time of five to ten days. Severe or complicated outbreaks may require longer treatment courses. Doxycycline/ tetracycline is also the preferred drug for patients with ehrlichiosis, another tick-transmitted infection with signs and symptoms that may resemble those of Rocky Mountain spotted fever.

Chloramphenicol is an alternative drug that can be used to treat Rocky Mountain spotted fever, specifically in pregnancy. However, this drug may be associated with a wide range of side effects, and careful monitoring of blood levels can be required.

The illness can be treated with tetracyclines (doxycycline is the preferred treatment), chloramphenicol, macrolides or fluoroquinolones.

Without treatment, the disease is often fatal. Since the use of antibiotics, case fatalities have decreased from 4–40% to less than 2%.

The drug most commonly used is doxycycline or tetracycline, but chloramphenicol is an alternative. Strains that are resistant to doxycycline and chloramphenicol have been reported in northern Thailand. Rifampicin and azithromycin are alternatives. Azithromycin is an alternative in children and pregnant women with scrub typhus, and when doxycycline resistance is suspected. Ciprofloxacin cannot be used safely in pregnancy and is associated with stillbirths and miscarriage.

Combination therapy with doxycycline and rifampicin is not recommended due to possible antagonism.

The disease can be fatal if left untreated, but endemic typhus is highly treatable with antibiotics. Most people recover fully, but death may occur in the elderly, severely disabled or patients with a depressed immune system. The most effective antibiotics include tetracycline and chloramphenicol. In United States, CDC recommends solely doxycycline.

Relapsing fever is easily treated with a one- to two-week-course of antibiotics, and most people improve within 24 hours. Complications and death due to relapsing fever are rare.

Tetracycline-class antibiotics are most effective. These can, however, induce a Jarisch–Herxheimer reaction in over half those treated, producing anxiety, diaphoresis, fever, tachycardia and tachypnea with an initial pressor response followed rapidly by hypotension. Recent studies have shown tumor necrosis factor-alpha may be partly responsible for this reaction.

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.

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.

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.

The infection is treated with antibiotics. Intravenous fluids and oxygen may be needed to stabilize the patient. There is a significant disparity between the untreated mortality and treated mortality rates: 10-60% untreated versus close to 0% treated with antibiotics within 8 days of initial infection. Tetracycline, Chloramphenicol, and doxycycline are commonly used. Infection can also be prevented by vaccination.

Some of the simplest methods of prevention and treatment focus on preventing infestation of body lice. Complete change of clothing, washing the infested clothing in hot water, and in some cases also treating recently used bedsheets all help to prevent typhus by removing potentially infected lice. Clothes also left unworn and unwashed for 7 days also cause both lice and their eggs to die, as they have no access to their human host. Another form of lice prevention requires dusting infested clothing with a powder consisting of 10% DDT, 1% malathion, or 1% permethrin, which kill lice and their eggs.

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.

Prevention of ATBF centers around protecting oneself from tick bites by wearing long pants and shirt, and using insecticides like DEET on the skin. Travelers to rural areas in Africa and the West Indies should be aware that they may come in contact with ATBF tick vectors. Infection is more likely to occur in people who are traveling to rural areas or plan to spend time participating in outdoor activities. Extra caution should be taken in November - April, when "Amblyomma" ticks are more active. Inspection of the body, clothing, gear, and any pets after time outdoors can help to identify and remove ticks early.

Doxycycline has been used in the treatment of rickettsial infection.

The American Public Health Association recommends treatment based upon clinical findings and before culturing confirms the diagnosis. Without treatment, death may occur in 10 to 60 percent of patients with epidemic typhus, with patients over age 60 having the highest risk of death. In the antibiotic era, death is uncommon if doxycycline is given. In one study of 60 hospitalized patients with epidemic typhus, no patient died when given doxycycline or chloramphenicol. Some patients also may need oxygen and intravenous (IV) fluids.

If ehrlichiosis is suspected, treatment should not be delayed while waiting for a definitive laboratory confirmation, as prompt doxycycline therapy has been associated with improved outcomes. Doxycycline is the treatment of choice.

Presentation during early pregnancy can complicate treatment.Rifampin has been used in pregnancy and in patients allergic to doxycycline.

Currently, there is no vaccine against human granulocytic anaplasmosis, so antibiotics are the only form of treatment. The best way to prevent HGA is to prevent getting tick bites.

Doxycycline and minocycline are the medications of choice. For people allergic to antibiotics of the tetracycline class, rifampin is an alternative. Early clinical experience suggested that chloramphenicol may also be effective, however, in vitro susceptibility testing revealed resistance.

Doxycycline is the treatment of choice. If anaplasmosis is suspected, treatment should not be delayed while waiting for a definitive laboratory confirmation, as prompt doxycycline therapy has been shown to improve outcomes. Presentation during early pregnancy can complicate treatment. Doxycycline compromises dental enamel during development. Although rifampin is indicated for post-delivery pediatric and some doxycycline-allergic patients, it is teratogenic. Rifampin is contraindicated during conception and pregnancy.

If the disease is not treated quickly, sometimes before the diagnosis, the person has a high chance of mortality. Most people make a complete recovery, though some people are intensively cared for after treatment. A reason for a person needing intensive care is if the person goes too long without seeing a doctor or being diagnosed. The majority of people, though, make a complete recovery with no residual damage.

Treatment of asymptomatic carriers should be considered if parasites are still detected after 3 months. In mild-to-moderate babesiosis, the treatment of choice is a combination of atovaquone and azithromycin. This regimen is preferred to clindamycin and quinine because side effects are fewer. The standard course is 7 to 10 days, but this is extended to at least 6 weeks in people with relapsing disease. Even mild cases are recommended to be treated to decrease the chance of inadvertently transmitting the infection by donating blood. In life-threatening cases, exchange transfusion is performed. In this procedure, the infected red blood cells are removed and replaced with uninfected ones.

Imizol is a drug used for treatment of babesiosis in dogs.

Extracts of the poisonous, bulbous plant "Boophone disticha" are used in the folk medicine of South Africa to treat equine babesiosis. "B. disticha" is a member of the daffodil family Amaryllidaceae and has also been used in preparations employed as arrow poisons, hallucinogens, and in embalming. The plant is rich in alkaloids, some of which display an action similar to that of scopolamine.

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.

Rocky Mountain spotted fever can be a very severe illness and patients often require hospitalization. Because "R. rickettsii" infects the cells lining blood vessels throughout the body, severe manifestations of this disease may involve the respiratory system, central nervous system, gastrointestinal system, or kidneys.

Long-term health problems following acute Rocky Mountain spotted fever infection include partial paralysis of the lower extremities, gangrene requiring amputation of fingers, toes, or arms or legs, hearing loss, loss of bowel or bladder control, movement disorders, and language disorders. These complications are most frequent in persons recovering from severe, life-threatening disease, often following lengthy hospitalizations

As of 2017 there is no commercially available vaccine. A vaccine has been in development for scrub typhus known as the scrub typhus vaccine.

Treatment usually involves a prescription of doxycycline (a normal dose would be 100 mg every 12 hours for adults) or a similar class of antibiotics. Oxytetracycline and imidocarb have also been shown to be effective. Supportive therapy such as blood products and fluids may be necessary.

No human vaccine is available for ehrlichiosis. Tick control is the main preventive measure against the disease. However, in late 2012 a breakthrough in the prevention of CME (canine monocytic ehrlichiosis) was announced when a vaccine was accidentally discovered by Prof. Shimon Harrus, Dean of the Hebrew University of Jerusalem's Koret School of Veterinary Medicine.