Neutropenia is a significant hematologic complication induced by cytotoxic chemotherapy. The clinical consequences of chemotherapy-induced neutropenia are often severe and can be potentially life-threatening. Patients who develop febrile neutropenia often need to be hospitalized, reducing their quality of life and increasing costs. Neutropenia can also compromise the ability to deliver chemotherapy at the full dose and on schedule. To help prevent the occurrence of neutropenia, patients with a high risk of developing chemotherapy-related infections may be given prophylactic colony-stimulating factors. Filgrastim is a recombinant human granulocyte colony-stimulating factor that has been widely used (in over 3 million patients) for over 12 years in the management of neutropenia. Pegfilgrastim is an approved, long-acting, next generation of granulocyte colony-stimulating factor that has similar clinical benefits to filgrastim but has novel pharmacokinetic properties. Pegfilgrastim shows at least comparable safety and efficacy to filgrastim, with the added benefit of simplified once-per-chemotherapy-cycle dosing. In addition, two randomized, controlled pivotal trials have shown that a single dose of pegfilgrastim given once per cycle led to a lower observed incidence of febrile neutropenia following myelosuppressive chemotherapy, compared with daily injections of filgrastim. Clinical trials are currently expanding the clinical experience with pegfilgrastim in a variety of solid tumors and hematologic malignancies. In addition to prevention of chemotherapy-induced neutropenia in 21- and 28-day regimens, future studies are examining the suitability of pegfilgrastim in dose-dense therapy and other cancer settings.