Dendritic cells (DC) are heterogenous, comprising several subpopulations of migratory and lymphoid-organ-resident types. Recent studies addressing the role of each subset in antigen presentation in vivo have revealed a complex division of labor within the DC network. In addition to CD8(+) DC, migratory lung or dermal DC can cross-present antigen in vivo. Migratory DC also transport to the lymph nodes antigens that can be transferred to resident DC for presentation. In inflammatory conditions, the antigen-presentation abilities of DC can be severely impaired, but an additional population of monocyte-derived DC then comes into play. Understanding the contribution of each DC subset to a physiological immune response is particularly relevant for rational vaccine design.