The optimum regimen for the treatment of cryptococcal meningitis in patients with AIDS is still not totally clear. The triazoles fluconazole and itraconazole are associated with response rates of 50%-60%. Amphotericin B appears to be associated with a more rapid clearance of organisms, and there are some data suggesting that initial therapy with amphotericin B is preferable to that with triazoles; however, this finding has not been definitively shown in large comparative trials. Results of a recently completed large trial suggested that initial treatment with amphotericin B followed by triazole therapy is associated with an acute mortality rate (approximately 6%) that is substantially less than that in previous studies. Relapse is common (20%-60% of cases) if the patient does not receive chronic suppressive therapy. The drug of choice for maintenance therapy is fluconazole (200 mg/d). A recent trial showed that fluconazole was superior to itraconazole (200 mg/d) as suppressive therapy. Prophylactic use of fluconazole (200 mg/d) significantly decreases the incidence of cryptococcosis and mucosal candidiasis, especially in patients with CD4 cell counts of < 50/mm3. However, because of the lack of a survival benefit and the risk of the selection effect on fluconazole-resistant Candida, it is difficult to make the recommendation of routine prophylaxis with fluconazole for all patients with AIDS; the decision to use prophylaxis should be based on more selective criteria.