The treatment of patients with HIV-related non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) is less successful than in the non-HIV setting, in part due to the aggressive character of these lymphomas but also due to the underlying HIV infection. High-dose therapy with stem cell transplantation has been used with success in the HIV-negative lymphoma setting for high-risk or relapsed disease. However, for patients with HIV-NHL and HIV-HD, ultimately the chance for long-term lymphoma-free survival also depends on successful control of the HIV infection. Gene therapy approaches may provide the opportunity for this long-term control. Herein, we describe the use of high-dose chemotherapy with stem cell rescue in conjunction with current and future gene therapy approaches for the treatment of HIV-associated lymphomas.