South Africa (SA) has the highest global incidence of human immune deficiency virus (HIV) infection with an estimated 6.4 million South Africans currently infected. Antiretroviral therapy (ART) rollout commenced in the public sector in 2004 and SA now has the largest ART therapy program in the world. Haematological complications of HIV are frequent and diverse, occurring at all stages of infection. Usually multiple factors contribute to the haematological derangements and a meticulous, logical approach including consideration of all possible contributors is needed. Anaemia is the most common cytopenia and may be due HIV related causes (such as anaemia of chronic disease, ART drug side effects or opportunistic infections) or HIV-unrelated causes (such as haematinic deficiencies or haemoglobinopathies). Immune thrombocytopenia, opportunistic infections (particularly tuberculosis) and drug side effects are also frequent causes of cytopenias. Common haematological emergencies occurring in this setting include Burkitt lymphoma, and thrombotic thrombocytopenia purpura. Tuberculosis (TB) is the leading cause of death in HIV infected patients in SA and is often associated with cytopenias and bone marrow involvement. A bone marrow biopsy has a high diagnostic yield in patients with unexplained cytopenias and/or fever and may provide a rapid diagnosis of involvement by TB or lymphoma.