Neoplastic disease is a frequent complication in patients with acquired immunodeficiency disease (AIDS) and other immunodeficiencies. Many such neoplasms are caused by either Epstein-Barr virus (EBV) or Kaposi's sarcoma-associated herpes virus (KSHV). The treatment of such patients can be challenging. At the same time, the viral origin of these tumors offers targets to develop pathogenesis-based therapies. Standard therapies for these diseases involve such approaches as treating the underlying immunodeficiency, cytotoxic chemotherapy, and immunologic antitumor therapy. Novel therapy approaches include specific immune therapy and anti-angiogenesis approaches, now under development.