Patients who become neutropenic secondary to chemotherapy for malignancy are at high risk for bacterial infection. Since the most common organisms include enteric gram-negative bacilli and staphylococci, drug combinations have traditionally been used. In addition, available clinical evidence suggests that synergistic drug combinations are most effective in the treatment of infections due to Pseudomonas aeruginosa. Comparative clinical trials have not shown any particular drug combination to be superior to others tested. Therefore, the drug choice for the combination should be based on local susceptibility patterns, clinical experience, and cost. Newer beta-lactam compounds are broader in spectrum and more potent than older drugs, and have been tested as sole agents in this setting. Although results appear promising for drugs such as cefoperazone or ceftazidime, the development of resistance and lack of adequate antistaphylococcal activity preclude routine use of these drugs. Imipenem is currently undergoing clinical trials for this purpose and appears to have the appropriate breadth of spectrum. However, frequent development of resistance among isolates of P. aeruginosa is problematic. At the present time a combination of an aminoglycoside and an extended-spectrum penicillin seems to be the therapy of choice for the febrile, neutropenic patient.