The patient with acute leukemia is predisposed to infection by bone marrow failure that leads to absence of granulocytes, by extramedullary leukemia infiltration that leads to barrier breakdown, and by cytotoxic antileukemia therapy that exaggerates both the hematopoietic and the tissue mucosal defects. Empiric approaches tailored to treat commonly occurring bacterial and fungal infections have successfully decreased the morbidity and mortality from overwhelming infection in these compromised patients. More recently, prophylaxis directed against dissemination of pathogens from specific sites has had a positive impact in preventing the clinical and microbiological manifestations of infection during profound aplasia. The approaches that have been successful in preventing and treating bacterial infections are being applied to the increasingly prevalent fungal infections that occur later during the granulocytopenic course, with encouraging results.