Cryptococcosis is a common opportunistic fungal disease in immunocompromised patients and also may occur in normal hosts. Cryptococcal disease most frequently involves the lungs and central nervous system. Management remains controversial, especially in patients with life-threatening disease and those with underlying T-cell dysfunction due to AIDS, neoplasia, or corticosteroid therapy. While amphotericin B, usually in combination with flucytosine, generally is recommended as primary therapy for patients with severe forms of disease, especially cryptococcal meningitis, alternative treatment regimens have been developed or are under investigation. These include the use of an oral triazole alone (fluconazole or itraconazole), an all-oral combination of fluconazole and flucytosine, and a novel induction-consolidation regimen using several drugs. Patients with AIDS are at high risk of relapse; consequently, chronic maintenance therapy is indicated. For patients with cryptococcal meningitis who have hydrocephalus or other central nervous system complications, aggressive adjunctive measures such as ventricular shunting must be employed. © 1993 by The University of Chicago.