Chemotherapy-induced neutropenia can cause complications that result in dose reductions or treatment delays that can, in turn, compromise clinical outcomes. Although the prophylactic use of colony-stimulating factors (CSFs) can reduce the risk, severity, and duration of severe and febrile neutropenia, they are not routinely administered to all patients undergoing myelosuppressive chemotherapy because of the costs. Selective use may, however, enhance their cost-effectiveness. These guidelines discuss the preventative or prophylactic use of recombinant human granulocyte-CSF to reduce the incidence, length, and severity of chemotherapy-related neutropenia and and prevent life-threatening complications. © Journal of the National Comprehensive Cancer Network.