The study of antigen-presenting cells (APC) in HIV pathogenesis has been ongoing for almost 20 years. The initial studies recognized the important role of APC as targets for HIV infection and their ability to serve as reservoirs of virus, particularly in tissues. The issue of whether HIV impacts the functional competency of APC has been more controversial, with some studies showing reduced expression of important costimulatory molecules on APC, but others showing the functional capacity of APC to be normal. The study of APC has advanced with recent interest in one class of APC, namely the dendritic cell. These cells have been shown to consist of numerous subsets and serve an important role in bridging innate and adaptive immune responses. The impact of HIV infection on dendritic cells has recently been characterized, as well as the critical functional role of these cells in host defenses in HIV-infected patients. One of the more exciting recent advances in APC biology is the ability to manipulate APC ex vivo for therapeutic purposes in an attempt to restore immune responses in HIV-infected persons. This review covers many of the advances of the field of APC biology and puts them into perspective with HIV pathogenesis.