Thrombocytopenia that is associated with infection due to human immunodeficiency virus (HIV) is an important and common hematologic abnormality. Although this condition is often asymptomatic, it may manifest clinically as a spectrum of bleeding problems including petechiae, ecchymoses, epistaxis, or menorrhagia or as hemorrhage of the gingivae, gastrointestinal tract, or CNS. Thrombocytopenia may be present in patients at any stage of immunodeficiency, and spontaneous remission can occur. We review the natural history of HIV-related thrombocytopenia and discuss treatment options.