AbstractDespite widely available antiretroviral therapy, lymphoma remains the leading cause of death for human immunodeficiency virus (HIV)–infected persons in economically developed countries. Even a few months of drug interruptions can lead to drops in the CD4 cell count, HIV viremia, and an increased risk of lymphoma. Currently, good HIV control facilitates intensive therapies appropriate to the lymphoma, including autologous and even allogeneic hematopoietic stem cell transplantation. Nonetheless, HIV-related lymphomas have unique aspects, including pathogenetic differences driven by the presence of HIV and often coinfection with oncogenic viruses. Future therapies might exploit these differences. Lymphoma subtypes also differ in the HIV-infected population, and the disease has a higher propensity for advanced-stage, aggressive presentation and extranodal disease. Other unique aspects include the need to avoid potential interactions between antiretroviral therapy and chemotherapeutic agents and the need for HIV-specific supportive care such as infection prophylaxis. Overall, the care of these patients has progressed sufficiently that recent guidelines from the American Society of Clinical Oncology advocate the inclusion of HIV-infected patients alongside HIV-negative patients in cancer clinical trials when appropriate. This article examines HIV lymphoma and includes Burkitt lymphoma in the general population.