The association of neutropenia and infection continues to be a major cause of morbidity and mortality in cancer patients receiving myelosuppressive chemotherapy. Prompt hospitalization and initiation of empirical intravenous broad-spectrum antibiotics has been the standard of care during the past three decades. Recently, risk-assessment models have been developed that allow the identification of febrile neutropenic patients that are at low risk for medical complications and mortality. New treatment strategies are being evaluated in this low-risk patient population to safely reduce toxicity, decrease costs, and improve quality of life. These include early shift from intravenous therapy to oral antibiotics, immediate initiation of oral empiric treatment, early hospital discharge, or outpatient care. A risk-based approach should also be applied to the use of colony-stimulating factors in this setting. Growth factors should not be routinely administered to neutropenic patients with uncomplicated febrile episodes. However, recent data support their use in populations with high-risk neutropenic fever.