Combination anti-retroviral therapy for HIV disease has profoundly altered the nature of the AIDS epidemic. Mitigating the impact of an uncontrollable decline in immune function is no longer the focal point for AIDS therapy, but has evolved to an emphasis on maximizing the potential for immune regeneration. Improved control of HIV replication has diminished, albeit unevenly, the frequency of AIDS-related malignancies and has altered the focus of hematologic and oncologic interventions in HIV disease. Now, with adoptive cellular therapies and the genetic engineering of cells in the clinical arena, the potential for cellular therapeutics in enhancing immune restoration is being tested. These approaches are based on better understanding of the immunobiology of HIV and its impact on hematopoietic tissues.