Burkitt lymphoma (BL) is a highly aggressive B-cell malignancy that occurs with increased frequency among patients infected with HIV. Until recently, the immunocompromised state of patients with HIV and BL was generally deemed to preclude the use of the intensive chemotherapeutic regimens used to treat HIV-negative patients due to toxicity issues. However, the advent of highly active antiretroviral therapy (HAART) and the mounting evidence that less intensive lymphoma regimens are ineffective in BL have led investigators to treat HIV-positive patients with the same chemotherapy now established as the standard of care for immunocompetent patients. Data suggest that these current approaches, along with supportive care, may result in improved patient outcomes. In contrast, the role of adjunctive immunotherapy with rituximab in HIV-BL remains undefined. Further studies, including randomized clinical trials, are needed to better delineate the optimal treatment for patients with this devastating disease.