The necessity for administering empirical antibiotic therapy to febrile neutropenic patients has been well-established; however, no single regimen has been uniformly accepted. During the past decade, gram-positive organisms, often methicillin-resistant, have emerged as significant pathogens. The routine use of vancomycin may be appropriate at some institutions, but its widespread use may lead to resistance. The role of aminoglycosides as part of routine empirical regimens is controversial, and single extended-spectrum beta-lactam agents are often adequate therapy. Not all beta-lactam agents are equally effective, and some gram-negative pathogens, such as Xanthomonas maltophilia, are resistant to many of them. Pneumonia is frequent, the infecting pathogen is often undetermined, and therapy is unsatisfactory. Outpatient antibiotic therapy can be used in selected neutropenic patients. Empirical antibiotic regimens should be selected on the basis of knowledge about predominant pathogens and antibiotic susceptibilities at each institution as much as on the basis of studies from other institutions reported in the literature.