Recently, anemia associated with human immunodeficiency virus (HIV) disease has received more attention as our understanding of the significance of anemia in this population has grown and more emphasis is placed on the quality of life of people living with HIV/AIDS. Although the diagnosis and treatment of anemia in HIV disease has been discussed in great detail, the prevalence and pathophysiology of the two most common forms of anemia, iron deficiency anemia (IDA) and the anemia of chronic disease (ACD), have not received much attention despite the difficulty and importance of differentiating between these two anemias. In addition, little attention has been given to iron overload, which has serious implications in individuals with HIV disease. This article proposes a model of altered iron metabolism in HIV disease as a basis for explaining the pathophysiology and implications of IDA, ACD, and iron overload in this population. Implications for clinical practice and recommendations for future research are discussed.