Granulocytopenia has been closely associated with cancer and its treatment. The risk for a life-threatening infection when the granulocyte count falls below 500/mm3 not only is an important complication of therapy and a major cause of death in cancer patients but also plays an important role in the design, schedule, and doses of cancer treatment regimens. While granulocytopenia remains an unavoidable complication of current therapy, improved recognition of patients at risk and prompt initiation of aggressive supportive care have had a significant impact on reducing its infection-related morbidity and mortality. In particular, early empiric antibiotic therapy when the granulocytopenic patient becomes febrile has resulted in a significant reduction in the early mortality from undiagnosed bacterial infections. New antibiotics (extended-spectrum penicillins, third generation cephalosporins) provide new options because of their broad efficacy and potential for reducing the toxicity of antimicrobial therapy. However, as bacterial infections have become better controlled, fungi have emerged as important pathogens. Early aggressive empiric antifungal therapy appears to have reduced infectious mortality, although the repertoire of effective antifungal agents is quite limited. Considerable efforts have been expended in trying to replenish granulocytes by transfusion in infected patients, but technical deficiencies have limited this approach. Current and future efforts are directed toward refining management as well as to developing methods to improve host defenses and provide prophylaxis against infections. If the full potential of current cancer therapy is to be realized, control of granulocytopenia and the prevention of infections are essential goals.