Recent progress in phenotyping of human dendritic cells (DCs) has allowed a closer alignment of the classification and functions of murine and human dendritic cell subsets. Marked differences in the functions of these human DC subsets and their response to HIV infection have become apparent, relevant to HIV pathogenesis and vaccine and microbicide development. Systems biology approaches to studying HIV uptake and infection of dendritic cells has revealed how markedly HIV subverts their functions, especially in relation to the trafficking pathways and viral transfer to T cells. Furthermore the interactions between DCs and other innate immune cells, NK cells, NKT cells and gamma delta T cells are now known to influence DC and T cell function and are also disturbed by HIV infection in vitro and in vivo. Such cellular interactions are potential targets for vaccine adjuvants and immunotherapy.