The colony-stimulating factors (CSFs) represent the only biological response modifiers used in clinical practice to treat or prevent neutropenia. These pleiotropic cytokines are available in clinical practice as granulocyte CSF (G-CSF), granulocyte-macrophage CSF (GM-CSF) and pegylated G-CSF. Neutropenia and its complications, most importantly febrile neutropenia (FN), remain major and serious side effects of cancer chemotherapy. Several studies and meta-analyses have addressed the clinical applications of CSFs to treat or prevent neutropenia. Guidelines have been developed to foster the appropriate use of CSFs. This article reviews the nature and use of the CSFs, and summarises the critical studies and guidelines. A historical perspective briefly describes the discovery, synthesis and clinical use of CSFs. The major biological and pharmacological characteristics are highlighted. The clinical applications of the CSFs are reviewed, including primary FN prophylaxis, secondary FN prophylaxis, treatment of FN, support of dose-dense chemotherapy regimens, use in leukaemia and myelodysplastic syndromes, utility in stem cell transplantation, and use in elderly and paediatric patients. Finally, clinical efficacy data, as well as the economic impact of the CSFs, are discussed.