Anemia is the most common hematologic manifestation of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome. The causes of HIV-related anemia are multifactorial and include direct and indirect effects of HIV infection. HIV-related anemia generally is due to reduced red blood cell (RBC) production, secondary to a variety of causes, but it may also involve nutritional deficiencies, increased RBC destruction, or a combination of these problems. Evaluation of hemoglobin level, reticulocyte count, bilirubin, and mean corpuscular volume value and review of the peripheral blood smear are necessary for diagnosis. Treatment of HIV-related anemia should address the correctable underlying causes of this disorder, such as modifications of offending medications, nutritional deficiencies, and parvovirus infection. Patients with HIV infection have a blunted erythropoietin response to anemia. Therapeutic modalities for anemia that is not amenable to correction include blood transfusion and recombinant human erythropoietin (epoetin alfa).