Febrile neutropenia (FN) continues to represent a major cause of morbidity, mortality, and cost in patients receiving cancer chemotherapy. The reported rates of FN vary considerably among studies depending on the treatment regimen, delivered dose intensity, and patient population. The risk of initial FN appears to be highest during the first cycle of chemotherapy and is greatest in certain high-risk groups including elderly patients and those with various comorbidities. Febrile neutropenia continues to have considerable clinical, economic, and quality-of-life impact on affected patients. The risk of mortality associated with FN continues to be relatively high in patients with hematologic malignancies, patients presenting with comorbid illnesses, and patients with bacteremia, pneumonia, or other infection-related complications. The reduction in chemotherapy dose intensity that frequently follows an episode of FN may have considerable life-threatening impact on disease control in responsive and potentially curable malignancies. The economic burden of FN is substantial, with the greatest proportion of the cost associated with the relatively limited number of patients hospitalized for prolonged periods as a result of comorbidities or complications. The colony-stimulating factors (CSFs) may reduce the risk and cost associated with cancer treatment by reducing the probability of hospitalization with FN. Primary prophylaxis with the CSFs may be warranted in patients receiving intensive regimens or in those at greater risk because of age or comorbidities. Further study of various risk factors for FN should help identify patients at greatest risk and likely candidates for targeted use of the hematopoietic growth factors.