Judicious use of myelopoietic colony-stimulating factors is not well defined and is the source of ongoing controversy in the pediatric patient population. Prophylactic colony-stimulating factors may provide little clinically relevant benefits in children with hematologic malignancies or solid tumors after myelosuppressive chemotherapy. Although several studies demonstrated that recombinant human granulocyte colony-stimulating factor and granulocyte macrophage colony-stimulating factor accelerate neutrophil engraftment after myeloablative therapy and stem cell transplantation, their use did not alter morbidity or mortality after stem cell transplantation and has been associated with delayed platelet engraftment. Large prospective randomized multicenter studies are necessary to demonstrate an improvement in infectious complications, duration of hospitalization, overall survival, and cost-benefit ratio with the prophylactic use of myelopoietic growth factors after myelosuppressive or myeloablative chemotherapy in children and adolescents. Additional pediatric studies comparing the safety, efficacy, and cost effectiveness of granulocyte colony-stimulating factor versus granulocyte macrophage colony-stimulating factor are needed.