Fluconazole is compared with other agents for antifungal prophylaxis in patients with chemotherapy-induced neutropenia. Fluconazole is an attractive alternative for antifungal prophylaxis because of its activity against many Candida species, long half-life, good patient tolerability, and minimal associated toxicity. The results of clinical trials suggest that fluconazole is superior to placebo and oral polyenes in preventing superficial fungal infection in neutropenic patients; however, its efficacy against systemic infection is not as strongly supported. Fluconazole use may increase emergence of resistant yeasts, particularly Candida krusei and Torulopsis glabrata. The cost of fluconazole 50 mg/day is similar to the costs of other antifungals used for prophylaxis; however, fluconazole 400 mg/day (the most frequently studied dose in neutropenic patients) is considerably more expensive. Comparative clinical trials between fluconazole and other antifungals are needed to determine which is superior for prophylaxis. Fluconazole is effective for prophylaxis against superficial fungal infection and may be an attractive alternative therapeutic regimen in patients undergoing bone marrow transplantation. In other neutropenic patients, such as those with leukemia, the superiority of fluconazole has not been substantiated; therefore, it is not recommended over other agents, such as clotrimazole and ketoconazole, at this time.