Dr. William G. Powderly provides a comprehensive review of the state of our knowledge regarding cryptococcal infection in persons with infection due to human immunodeficiency virus type 1. The introduction of fluconazole and itraconazole increased insight into prognostic factors affecting these patients. The need to suppress this fungal infection in individuals with impaired immunity has greatly altered the management of cryptococcal meningitis; therapy for this condition was established by the landmark study conducted by the Mycosis Study Group in 1979 (Bennett JE, Dismukes WE, Duma RJ, et al. A comparison of amphotericin B alone and combined with flucytosine in treatment of cryptococcal meningitis. N Engl J Med 1979;301:126-31). In this AIDS commentary Dr. Powderly clearly outlines the progress made through clinical investigations and the problems that remain to be resolved.