OBJECTIVE The center of gravity of the AIDS epidemic has moved - in 2007, 67% of all persons living with HIV infection and 72% of all deaths from AIDS occurred in Africa. The present review focuses on the treatment of an AIDS-defining malignancy, Burkitt lymphoma, since the discovery of the tumor in 1958 to provide a backdrop to the increasing necessity of dealing with AIDS-associated Burkitt lymphoma in Africa. RESULTS In Africa, it appears that AIDS-associated Burkitt lymphoma is increasing, but although treatment outcome is presently poor, the demonstration that highly active antiretroviral therapy permits the same treatment results to those in AIDS-unassociated Burkitt lymphoma provides hope for the future. CONCLUSIONS In the 1960s, the extraordinary response of Burkitt lymphoma to chemotherapy provided considerable encouragement to pioneer oncologists. Within little more than a decade, the most active drugs, the value of combination chemotherapy, and the need for intrathecal treatment, as well as the risk of tumor lysis syndrome had been demonstrated, providing a platform on which further advances could be made in resource-rich countries. Since that time, little progress has been made in Africa, but recent collaborative projects have shown that improved treatment outcome can be achieved at low cost. The impact of the HIV epidemic on the epidemiology and treatment of African Burkitt lymphoma will receive increasing focus in the coming years.