Both cryptococcosis and histoplasmosis are life-threatening diseases in patients with advanced HIV infection. Cryptococcal disease in patients with AIDS is usually a systemic illness with an insidious onset of meningoencephalitis. Development of potent oral antifungal agents has simplified therapy, although patients with cryptococcal meningitis are at high risk for relapse. Histoplasmosis is usually disseminated in AIDS patients. Definitive diagnosis requires culture of the pathogen from blood or other specimens. Although availability of azole compounds has broadened treatment options, relapse is common after treatment of acute disease, and lifelong suppressive oral therapy is needed. Antifungal prophylaxis is not considered cost-effective at this time.