Febrile neutropenia (FN) can occur at any time during the course of a malignancy, especially hematologic malignancies, from diagnosis to end-stage disease. The majority of FN episodes are typically confined to the period of initial diagnosis and active treatment. Because of suppressed inflammatory responses, fever is often the sole sign of infection. As FN is a true medical emergency, prompt identification of and intervention in FN can prolong survival and improve quality of life. This article reviews FN in the setting of hematologic malignancies, specifically myelodysplastic syndromes and acute leukemias, providing an overview of the definition of fever and neutropenia, diagnostic approach, categories of risk/risk assessment, management in patients at low and high risk, and prophylaxis of infections.