There has been considerable interest in the role of the lymphoma microenvironment. Despite the use of highly active antiretroviral therapy (HAART), AIDS-related diffuse large-B-cell lymphoma remains common and HIV-associated classical Hodgkin’s lymphoma is increasing in incidence. Less is known about the impact HIV and HAART have on the lymphoma microenvironment. AIDS-related diffuse large B-cell lymphoma is highly angiogenic, demonstrates increased lymphoblastic histology, proliferation, increased activated cytotoxic T cells, reduced CD4+ and FOXP3+ T cells, but no differences in tumor-associated macrophages. Early initiation of HAART improves immunosurveillance, but cases without viral antigens appear able to avoid immunologic reaction. Increased T cell infiltrates seen with HAART treatment in HIV-related classical Hodgkin’s lymphoma may contribute to malignant cell growth.