Dendritic cells (DCs) are potent antigen sensing and presenting cells, able to both initiate and orchestrate complex immune responses. DCs are optimally equipped to recognize pathogens, as well as self-antigens and vaccine components, and instruct the type, magnitude and specificity of the ensuing immunity. However, the DC population is remarkably heterogeneous and consists of multiple subsets with different ontogeny, differentiation and functional specializations. Therefore, a deeper understanding of DC subset biology is fundamental for the development and implementation of innovative vaccination strategies.