Much attention has been focused in recent years on ways of optimizing the use and cost-effectiveness of erythropoietin therapy. The balance of evidence suggests that the subcutaneous route allows lower doses to be used compared with the intravenous route, and dosing should be two to three times weekly. Concomitant use of intravenous iron potently enhances the response to erythropoietin, and more recently other adjuvant therapies such as ascorbic acid, L-carnitine, folic acid, vitamin D, androgens, and other cytokines and growth factors have been investigated. Many factors can affect the response to erythropoietin, and underdialysis and co-administration of angiotensin converting enzyme inhibitors have attracted much recent interest. Controversy regarding the optimum target hemoglobin concentration in patients with renal failure remains, but three multicenter studies are providing useful data on this issue.