Anemia is the most frequently encountered hematologic complication in human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome. The prevalence estimates vary widely with the severity of HIV disease. Data suggest that treatment with highly active antiretroviral therapy may have a positive impact on reducing the prevalence of anemia of chronic disease in patients infected with HIV. Anemia consistently has been shown to be a predictor of decreased survival, and treatment plays an important role in improving patients' survival and quality of life (e.g., fatigue and dementia). Addressing potential underlying reversible causes and treating the chronic anemia are important strategies in the management of anemia. Erythropoietin therapy should be considered a first-line treatment, and blood transfusions should be limited to situations requiring immediate correction of hemoglobin levels.