Although few in number, dendritic cells (DCs) are heterogeneous, ubiquitous, and are crucial for protection against pathogens. In this review, the different DC subpopulations have been described and aspects of DC biology are discussed. DCs are important, not only in the pathogenesis of HIV, but also in the generation of anti-HIV immune responses. This review describes the roles that DC are thought to play in HIV pathogenesis, including uptake and transport of virus. We have also discussed the effects that the virus exerts on DCs such as infection and dysfunction. Then we proceed to focus on DC subsets in different organs and show how widespread the effects of HIV are on DC populations. It is clear that the small number of studies on tissue-derived DCs limits current research into the pathogenesis of HIV. J. Leukoc. Biol. 80: 1001-1012; 2006.