HIV and malaria kill millions of people every year. They share a common geographic distribution, and both cause far more disease and death in sub-Saharan Africa than they do in the rest of the world. Many epidemiologic studies have suggested that HIV and malaria coexist independently, but some recent reports describe synergistic interactions between them. People living with HIV infection who do not have pre-existing immunity to malaria experience a marked increase in malaria severity. But for those who have acquired immunity through natural exposure to malaria, HIV-related immunosuppression is associated with only a modest increase in clinical malaria, which may be explained in part by more frequent nonmalaria febrile episodes. The effect of malaria infection on HIV disease progression due to increased viral replication may be important but has not yet been fully explored.