Dendritic cells (DCs) act as sentinels in peripheral tissues, continuously scavenging for antigens in their immediate surroundings. Their involvement in T cell responses is generally thought to consist of a linear progression of events, starting with capture of antigen in peripheral tissues such as the skin followed by migration to draining lymphoid organs and MHC-restricted presentation of antigen-derived peptide to induce T cell priming. The role of tissue-derived DCs in the direct priming of immune responses has lately been challenged. It now appears that, at least in some instances, a non-migratory subtype of DCs in the secondary lymphoid tissue presents tissue-derived antigen to T cells. Here, we review recent developments in research on DC function in the priming of immune responses.