Patients infected with human immunodeficiency virus (HIV) are at greater risk of developing non-Hodgkin lymphoma than the general population and aggressive B-cell lymphoma has become one of the most common of the initial acquired immunodeficiency syndrome (AIDS)-defining illnesses. This review considers the prognostic factors and new approaches to the treatment of patients with AIDS-related lymphoma (ARL). As highly active antiretroviral therapy (HAART) became available, the survival of many ARL patients has become comparable to that of HIV-negative patients. This is partly due to the decrease in the incidence of opportunistic infections and improved prognosis. Both developments can also be attributed to new treatment strategies for ARL, such as the use of effective infusional regimens, Rituximab combinations and high-dose therapy with autologous stem-cell transplantation for relapsed disease. However, unresolved issues persist, such as the optimal therapy for patients with Burkitt ARL or central nervous system involvement.