Healthcare costs continue to rise and hospitalization represents the single largest component of direct medical costs associated with cancer care. Neutropenia and its complications, including febrile neutropenia (FN), remain the major dose-limiting toxicity of systemic cancer chemotherapy. Although under-reported, FN often occurs early in the course of chemotherapy and contributes substantially to the morbidity, mortality, and cost of treatment. The risk of FN and its complications are associated with treatment intensity, age, and various comorbidities. Myeloid growth factors (MGFs) have been used effectively in a variety of clinical settings to prevent or treat FN and assist patients receiving dose-intensive chemotherapy with or without stem cell support. A meta-analysis of the available randomized controlled trials has confirmed the efficacy of prophylactic MGFs. The cost of these agents, along with their large-scale clinical use, has prompted several economic investigations. Economic models based on measures of resource use derived from randomized controlled trials have provided estimates of expected treatment costs, along with FN risk threshold estimates for the cost-saving use of prophylactic MGF. Recent studies have demonstrated the potential value of targeting MGFs toward patients at greatest risk based on accurate and valid predictive models. Although an emerging role has become apparent for MGFs in managing adult leukemia and supporting high-dose therapy with stem cell transplantation in adults, their value in the support of children in these settings remains unclear. Continuing clinical and economic evaluation, along with an updating of clinical practice guidelines because of rapid technologic and clinical advances, is encouraged.