Anemia, a common complication of HIV infection, is associated with morbidity and shortened survival. HIV-associated anemia can often be corrected with erythropoietin (EPO) therapy, which is safer than blood transfusion. Because the response to erythropoietin may be impaired by a number of treatable factors, all HIV patients with anemia should undergo careful evaluation for these factors. This article reviews evaluation and treatment strategies to maximize response to EPO and thus limit the need for blood transfusion.