Severe neutropenia and its related infectious complications remain a permanent threat for patients receiving intensive chemotherapy, especially in the context of bone marrow transplantation. Chemoprophylaxis and use of colony-stimulating factors have altered the severity of the clinical picture in a favorable direction: neutropenia can be shortened, and gram-negative infection can be made less frequent; neither can be yet abolished. Early therapy, eg, empiric combination treatment, remains the cornerstone of our approach to febrile neutropenia; the actual choice of agents is probably less important and should be guided by local epidemiologic conditions. The concepts of empiric therapy also starts to be more widely accepted for the control of fungal and viral infections. Finally, it is fair to recognize that, at the other end of the spectrum of febrile neutropenia, conventional chemotherapy that results in only moderate and short neutropenia can usually be managed without much problem, namely with broad-spectrum monotherapy. Other possible simplified approaches should be investigated under controlled conditions and in patients selected on the basis of favorable prognostic factors.