Infection is the major cause of death in neutropenic patients. Because of the lack of acute inflammatory cells, the usual signs of infection are often absent in these patients. Therefore, unexplained fever in a neutropenic patient requires prompt initiation of antibiotic therapy. Many physicians advocate continuing antibiotic therapy until neutropenia resolves. However, prolonged treatment with broad-spectrum antibiotics increases the risks of drug toxicity and superinfection with resistant bacteria and fungi. Based on a critical review of the literature and a large personal clinical experience, I offer tentative guidelines for withdrawing antibiotic therapy in persistently neutropenic patients. When antibiotic therapy is discontinued, frequent and careful monitoring of these patients and a low threshold for reinstituting antibiotic therapy are essential.