The localization of effector T cells to extralymphoid tissues is crucial for the generation of an effective immune response, but it also underlies many autoimmune and inflammatory disorders. Recent studies have highlighted a central role for draining lymph nodes and environmentally imprinted dendritic cells in the generation of tissue-tropic effector T cells. Here, I outline our current understanding of the mechanisms that regulate the generation and localization of tissue-tropic effector T cells, and the potential ways in which these pathways can be exploited for immunotherapeutic purposes.