Over time, the spectrum of the acquired immune deficiency syndrome (AIDS) epidemic has changed, especially with the advent of highly active antiretroviral therapy (HAART), The goal of this article is to delineate changes occurring in the incidence and management of lymphoma over the course of the AIDS epidemic. Lymphoma usually occurs rather late in the course of human immunodeficiency virus (HIV) infection and is the cause of death in up to 20% of HIV-infected individuals, It is seen in all population groups at risk for HN and is more common in men than in women, It is usually diagnosed in patients with markedly decreased CD4 cell counts, consistent with prolonged periods of HIV infection and subsequent immunosuppression, Recent data from several large series have demonstrated a substantial decline in the median CD4 cell count among patients with newly diagnosed AIDS-related lymphoma despite the recent widespread use of HAART. While still somewhat controversial, use of HAART has generally not produced a significant decline in the incidence of AIDS-related lymphoma. Patients treated with low-dose vs standard-dose chemotherapy for AIDS-related lymphoma have achieved similar response and survival rates, although standard-dose therapy is associated with greater toxicity. Adapting therapy to prognostic factors has not produced a significant improvement in survival. Use of antiretroviral therapy along with chemotherapy appears safe, and may be associated with longer survival, An infusional regimen called EPOCH (etoposide, prednisone, vincristine [Oncovin], cyclophosphamide, doxorubicin HCl) shows promise in the future management of AIDS-related lymphoma, No regimen is currently considered the standard of therapy for patients with relapsed AIDS-related lymphoma, and survival is short in this setting.