Antifungal drugs are used to treat mycoses. Depending on the nature of the infection, a topical or systemic agent may be used.

Example of antifungals include: fluconazole which is the basis of many over-the-counter antifungal treatments. Another example is amphotericin B which is more potent and used in the treatment of the most severe fungal infections that show resistance to other forms of treatment and it is administered intravenously.

Drugs to treat skin infections are the azoles: ketoconazole, itraconazole, terbinafine among others.

Yeast infections in the vagina, caused by "Candida albicans", can be treated with medicated suppositories such as tioconazole and pessaries whereas skin yeast infections are treated with medicated ointments.

Keeping the skin clean and dry, as well as maintaining good hygiene, will help larger topical mycoses. Because fungal infections are contagious, it is important to wash after touching other people or animals. Sports clothing should also be washed after use.

Treatment depends on the type of opportunistic infection, but usually involves different antibiotics.

Treatment options in persons without HIV-infection have not been well studied. Intravenous Amphotericin B combined with flucytosine by mouth is recommended.

Persons living with AIDS often have a greater burden of disease and higher mortality (30-70% at 10-weeks), but recommended therapy is with amphotericin B and flucytosine. Where flucytosine is not available (many low and middle income countries), fluconazole should be used with amphotericin. Amphotericin-based induction therapy has much greater microbiologic activity than fluconazole monotherapy with 30% better survival at 10-weeks. Based on a systematic review of existing data, the most cost-effective induction treatment in resource-limited settings appears to be one week of amphotericin B coupled with high-dose fluconazole. After initial induction treatment as above, typical consolidation therapy is with oral fluconazole for at least 8 weeks used with secondary prophylaxis with fluconazole thereafter.

The decision on when to start treatment for HIV appears to be very different than other opportunistic infections. A large multi-site trial supports deferring ART for 4–6 weeks was overall preferable with 15% better 1-year survival than earlier ART initiation at 1–2 weeks after diagnosis. A Cochrane review also supports the delayed starting of treatment until cryptococcosis starts improving with antifungal treatment.

Individuals at higher risk are often prescribed prophylactic medication to prevent an infection from occurring. A patient's risk level for developing an opportunistic infection is approximated using the patient's CD4 T-cell count and sometimes other markers of susceptibility. Common prophylaxis treatments include the following:

Sulfonamides are the traditional remedies to paracoccidiodomycosis. They were introduced by Oliveira Ribeiro and used for more than 50 years with good results. The most-used sulfa drugs in this infection are sulfadimethoxime, sulfadiazine, and co-trimoxazole. This treatment is generally safe, but several adverse effects can appear, the most severe of which are the Stevens-Johnson syndrome and agranulocytosis. Similarly to tuberculosis treatment, it must be continued for up to three years to eradicate the fungus, and relapse and treatment failures are not unusual.

Antifungal drugs such as amphotericin B or itraconazole and ketoconazole are more effective in clearing the infection, but are limited by their cost when compared with sulfonamides.During therapy, fibrosis can appear and surgery may be needed to correct this. Another possible complication is Addisonian crisis. The mortality rate in children is around 7-10%.

Fumagillin has been used in the treatment.

Another agent used is albendazole.

In bovines, an infestation is difficult to cure, as systemic treatment is uneconomical. Local treatment with iodine compounds is time-consuming, as it needs scraping of crusty lesions. Moreover, it must be carefully conducted using gloves, lest the worker become infested.

Treatment is not necessary since the lesion is benign, however the person may have esthetic concerns about the appearance. The condition often resolves rapidly with high dose acyclovir or desiclovir but recurs once this therapy is stopped, or as the underlying immunocompromise worsens. Topical use of podophyllum resin or retinoids has also been reported to produce temporary remission. Antiretroviral drugs such as zidovudine may be effective in producing a significant regression of OHL. Recurrence of the lesion may also signify that highly active antiretroviral therapy (HAART) is becoming ineffective.

Treatment requires both systemic oral treatment with most of the same drugs used in humans—terbinafine, fluconazole, or itraconazole—as well as a topical "dip" therapy.

Because of the usually longer hair shafts in pets compared to those of humans, the area of infection and possibly all of the longer hair of the pet must be clipped to decrease the load of fungal spores clinging to the pet's hair shafts. However, close shaving is usually not done because nicking the skin facilitates further skin infection.

Twice-weekly bathing of the pet with diluted lime sulfur dip solution is effective in eradicating fungal spores. This must continue for 3 to 8 weeks.

Washing of household hard surfaces with 1:10 household sodium hypochlorite bleach solution is effective in killing spores, but it is too irritating to be used directly on hair and skin.

Pet hair must be rigorously removed from all household surfaces, and then the vacuum cleaner bag, and perhaps even the vacuum cleaner itself, discarded when this has been done repeatedly. Removal of all hair is important, since spores may survive 12 months or even as long as two years on hair clinging to surfaces.

Cryptococcosis is a very subacute infection with a prolonged subclinical phase lasting weeks to months in persons with HIV/AIDS before the onset of symptomatic meningitis. In Sub-Saharan Africa, the prevalence rates of detectable cryptococcal antigen in peripheral blood is often 4–12% in persons with CD4 counts lower than 100 cells/mcL.

Cryptococcal antigen screen and preemptive treatment with fluconazole is cost saving to the healthcare system by avoiding cryptococcal meningitis. The World Health Organization recommends cryptococcal antigen screening in HIV-infected persons entering care with CD4<100 cells/μL. This undetected subclinical cryptococcal (if not preemptively treated with anti-fungal therapy) will often go on to develop cryptococcal meningitis, despite receiving HIV therapy. Cryptococcosis accounts for 20-25% of the mortality after initiating HIV therapy in Africa. What is effective preemptive treatment is unknown, with the current recommendations on dose and duration based on expert opinion. Screening in the United States is controversial, with official guidelines not recommending screening, despite cost-effectiveness and a 3% U.S. cryptococcal antigen prevalence in CD4<100 cells/μL.

The current first-line treatment is fluconazole, 200 mg. on the first day, followed by daily dosing of 100 mg. for at least 21 days total. Treatment should continue for 14 days after relief of symptoms.

Other therapy options include:

- nystatin is not an effective treatment for esophageal candidiasis. It can be used as (swish, do not swallow) treatment for oral candidiasis that occurs with the use of asthma pumps.

- other oral triazoles, such as itraconazole

- caspofungin, used in refractory or systemic cases

- amphotericin, used in refractory or systemic cases

Fungal pneumonia can be treated with antifungal drugs and sometimes by surgical debridement.

Oral candidiasis can be treated with topical anti-fungal drugs, such as nystatin, miconazole, Gentian violet or amphotericin B.

Underlying immunosuppression may be medically manageable once it is identified, and this helps prevent recurrence of candidal infections.

Patients who are immunocompromised, either with HIV/AIDS or as a result of chemotherapy, may require systemic treatment with oral or intravenous administered anti-fungals.

If candidiasis is secondary to corticosteroid or antibiotic use, then use may be stopped, although this is not always a feasible option. Candidiasis secondary to the use of inhaled steroids may be treated by rinsing out the mouth with water after taking the steroid. Use of a spacer device to reduce the contact with the oral mucosa may greatly reduce the risk of oral candidiasis.

In recurrent oral candidiasis, the use of azole antifungals risks selection and enrichment of drug-resistant strains of candida organisms. Drug resistance is increasingly more common and presents a serious problem in persons who are immunocompromised.

Prophylactic use of antifungals is sometimes employed in persons with HIV disease, during radiotherapy, during immunosuppressive or prolonged antibiotic therapy as the development of candidal infection in these groups may be more serious.

The candidal load in the mouth can be reduced by improving oral hygiene measures, such as regular toothbrushing and use of anti-microbial mouthwashes. Since smoking is associated with many of forms of oral candidiasis, cessation may be beneficial.

Tinea cruris is best treated with topical antifungal medications of the allylamine or azole type. The evidence is best for terbinafine and naftifine but other agents may also work.

The benefits of the use of topical steroids in addition to an antifungal is unclear. There might be a greater cure rate but no guidelines currently recommend its addition. The effect of Whitfield's ointment is also unclear.

Good denture hygiene involves regular cleaning of the dentures, and leaving them out of the mouth during sleep. This gives the mucosa a chance to recover, while wearing a denture during sleep is often likened to sleeping in one's shoes. In oral candidiasis, the dentures may act as a reservoir of Candida species, continually reinfecting the mucosa once antifungal medication is stopped. Therefore, they must be disinfected as part of the treatment for oral candidiasis. There are commercial denture cleaner preparations for this purpose, but it is readily accomplished by soaking the denture overnight in a 1:10 solution of sodium hypochlorite (Milton, or household bleach). Bleach may corrode metal components, so if the denture contains metal, soaking it twice daily in chlorhexidine solution can be carried out instead. An alternative method of disinfection is to use a 10% solution of acetic acid (vinegar) as an overnight soak, or to microwave the dentures in 200mL water for 3 minutes at 650 watts. Antifungal medication can also be applied to the fitting surface of the denture before it is put back in the mouth. Other problems with the dentures, such as inadequate occlusal vertical dimension may also need to be corrected in the case of angular cheilitis.

Available treatment falls into two modalities: treating infections and boosting the immune system.

Prevention of Pneumocystis pneumonia using trimethoprim/sulfamethoxazole is useful in those who are immunocompromised. In the early 1950s Immunoglobulin(Ig) was used by doctors to treat patients with primary immunodeficiency through intramuscular injection. Ig replacement therapy are infusions that can be either subcutaneous or intravenously administrated, resulting in higher Ig levels for about three to four weeks, although this varies with each patient.

Medical professionals recommend a preventative based approach of stopping fungus before it occurs. Prevention is preferable over a reactive treatment approach. The preventative based approach involves removing heat and moisture to the groin area.

- Dry off with a clean towel immediately after showering, swimming or perspiring.

- Shower after physical activities.

- Wear underwear with high air and moisture permeability fabric, such as linen (flax).

Extensive treatments have been used on domestic animals more than on wild animals, probably because infected domestic animals are easier to identify and treat than infected wildlife. Treatment plans and management vary across taxa because this disease tends to affect each species differently. Antifungal drugs are the first line of defense to kill the agents causing phaeohyphomycosis, but despite the significant progress made in the last two decades and a 30% increase in available antifungal drugs since 2000, many drugs are not effective against black fungi. Diseases caused black fungi are hard to treat because the fungi are very difficult to kill. This high resilience may be contributed to the presence of melanin in their cell walls. Current antifungal agents the fungi are not resistant to are posaconazole, voriconazole, and azole isavuconazole.

In 2006, a free-living Eastern box turtle, "Terrapene carolina carolina", was found with a form of phaeohyphomycosis and was brought in the Wildlife Center of Virginia. Its symptom was swelling of the right hindfoot; it was diagnosed as having chromomycosis by histopathology. The center provided a series of antimicrobial treatments and a one-month course of 1 mg itraconazole, administered orally once a day. The eastern box turtle was euthanized due to further complications and the caretakers’ belief that the turtle would not be able to survive if placed back in the wild.

A recent case of a form of phaeohyphomycosis infection was found in a dog in 2011. The Journal of the American Veterinary Medical Association published a case study in which researchers successfully managed an intracranial phaeohyphomycotic fungal granuloma in a one-year-old male Boxer dog. Veterinarians of the Department of Veterinary Clinical Sciences at Tufts University surgically removed the granuloma in the right cerebral hemisphere. The patient was treated with fluconazole for 4 months, and was followed with voriconazole for 10 months. Both are medications used to treat fungal infections. Based on magnetic resonance imaging and cerebrospinal fluid (CSF) analysis 8 months after the surgery, the male Boxer’s outcome was considered excellent.

Emphasis has been placed on how to manage this disease through careful management practices including: proper handling, preventing crowding situation with animals, and transportation. Both the animals and the environment should be treated thoroughly to hinder the spread and control the fungal infection. This is especially important since humans can also contract this disease.

The oral lesion itself is benign and self-limiting, however this may not necessarily be the case for the underlying cause of immunocompromise. For instance, OHL with HIV/AIDS is a predictor of bad prognosis, (i.e. severe immunosuppression and advanced disease).

There have been too few cases of TS reported for a standard treatment to be established. In some cases, improvement in immune function has been noted to produce spontaneous improvement in TS symptoms. This pattern is consistent with the behavior of other viral diseases found in immunocompromised patients, most relevantly with the nephropathy associated in kidney transplant recipients with the polyomavirus BK virus. Antiviral drugs such as valganciclovir and cidofovir have shown benefit in treating this disorder in case reports.

It is currently recommended that HIV-infected individuals with TB receive combined treatment for both diseases, irrespective of CD4+ cell count. ART (Anti Retroviral Therapy) along with ATT (Anti Tuberculosis Treatment) is the only available treatment in present time. Though the timing of starting ART is the debatable question due to the risk of immune reconstitution inflammatory syndrome (IRIS). The advantages of early ART include reduction in early mortality, reduction in relapses, preventing drug resistance to ATT and reduction in occurrence of HIV-associated infections other than TB. The disadvantages include cumulative toxicity of ART and ATT, drug interactions leading to inflammatory reactions are the limiting factors for choosing the combination of ATT and ART.

A systematic review investigated the optimal timing of starting antiretroviral therapy in adults with newly diagnosed pulmonary tuberculosis. The review authors included eight trials, that were generally well-conducted, with over 4500 patients in total. The early provision of antiretroviral therapy in HIV-infected adults with newly diagnosed tuberculosis improved survival in patients who had a low CD4 count (less than 0.050 x 109 cells/L). However, such therapy doubled the risk for IRIS. Regarding patients with higher CD4 counts (more than 0.050 x 109 cells/L), the evidence is not sufficient to make a conclusion about benefits or risks of early antiretroviral therapy.

The most common method of treatment includes radiotherapy and/or surgical excision .

If not treated, pemphigus can be fatal, usually from overwhelming opportunistic infection of lesions. The most common treatment is the administration of oral steroids, especially prednisone, often in high doses. The side effects of corticosteroids may require the use of so-called steroid-sparing or adjuvant drugs. One of the most dangerous side effects of high dosage steroid treatments is intestinal perforations, which may lead to sepsis. Steroids and other medications being taken to treat Pemphigus may also mask the effects of the perforations. Patients on high dosages of oral steroids should closely monitor their GI health. As lesions are usually terribly painful, it is likely that pain medication can complicate and exacerbate the GI issues caused by steroids.

In immunocompromised patients, prophylaxis with co-trimoxazole (trimethoprim/sulfamethoxazole), atovaquone, or regular pentamidine inhalations may help prevent PCP.

Antipneumocystic medication is used with concomitant steroids in order to avoid inflammation, which causes an exacerbation of symptoms about four days after treatment begins if steroids are not used. By far the most commonly used medication is trimethoprim/sulfamethoxazole, but some patients are unable to tolerate this treatment due to allergies. Other medications that are used, alone or in combination, include pentamidine, trimetrexate, dapsone, atovaquone, primaquine, pafuramidine maleate (under investigation), and clindamycin. Treatment is usually for a period of about 21 days.

Pentamidine is less often used as its major limitation is the high frequency of side effects. These include acute pancreatic inflammation, kidney failure, liver toxicity, decreased white blood cell count, rash, fever, and low blood sugar.