Invasive fungal infections are important causes of morbidity and mortality among patients with neoplastic diseases, particularly those with protracted granulocytopenia, those receiving corticosteroids, and those undergoing allogeneic bone marrow transplantation. These mycoses are often difficult to diagnose early, and their treatment is frequently unsuccessful. Antifungal compounds have been used in studies of a variety of preventive strategies including prophylaxis, early empirical therapy, empirical therapy, and secondary prophylaxis. Among all compounds studied thus far, fluconazole has demonstrated the most promising activity in prevention of invasive candidiasis, particularly in adult allogeneic bone marrow transplant recipients. However, fluconazole does not have activity at currently approved dosages against Candida krusei, Torulopsis glabrata, and most filamentous fungi, including Aspergillus species. Empirically administered amphotericin B significantly decreases the frequency of invasive fungal infections in persistently or recurrently febrile granulocytopenic patients. The use of itraconazole for prevention of aspergillosis warrants study. The current lack of reliable preventive regimens against infections due to Aspergillus and against those due to several emerging fungal pathogens presents an ongoing challenge. The use of recombinant human cytokines, transfusion of effector cells, and administration of newer antifungal compounds are new potential modalities for prevention of invasive mycoses.