Persons with HIV infection are at an increased risk of developing intermediate and high-grade non-Hodgkin's lymphomas. Patients present with wide-spread extranodal disease at the time of initial presentation, with unusual sites of disease common. Factors predictive of a poor prognosis are low performance status, history of AIDS prior to the diagnosis of lymphoma, bone marrow involvement, and low CD4 count. Experience suggests that in some patients, more aggressive chemotherapy may be associated with shortened survival time. Recent clinical trials have demonstrated that the use of either myeloid growth factors or reduced-dosage chemotherapeutic regimens can reduce the morbidity associated with chemotherapy. A number of new and exciting experimental treatments are now in clinical development. These include new chemotherapy-based regimens, immune modulators immunotoxin therapy, and cellular therapy. It is hoped that as we continue to learn more about the biology of the HIV-associated lymphomas, we can develop more rational and effective treatment modlities that take advantage of the unique molecular characteristics of these tumors.