Antiretroviral therapy has changed the face of the treatment of HIV throughout the world, converting a fatal into a chronic disease. HIV has reached disastrous levels of infection in southern Africa, and increased use of life-saving therapy is being implemented. The antiretrovirals have a variety of metabolic side effects that have been implicated in cardiovascular disease in other populations. This article discusses the impact of HIV on southern Africa, the metabolic and cardiac complications of both HIV and antiretrovirals, and strategies for dealing with drug side effects.