The erythropoietin analogs have been an important advance for the treatment of the anemia of kidney disease, resulting in reduced need for blood transfusion and improved quality of life. Recent studies, however, have indicated risks associated with targeting higher levels of hemoglobin (Hb). As a result, in March 2007, the US Food and Drug Administration (FDA) substantially changed prescribing information for these drugs to alert clinicians to these risks. In this review, we consider the recent literature, the change in FDA warnings, and new National Kidney Foundation Anemia Guidelines. Suggestions for new Hb targets during erythropoiesis-stimulating agent treatment are presented.