Coordinated migratory events are required for the development of effective and regulated immunity. Naïve T lymphocytes are programmed to recirculate predominantly in secondary lymphoid tissue by non-specific stimuli. In contrast, primed T cells must identify specific sites of antigen location in non-lymphoid tissue to exert targeted effector responses. Following priming, T cells acquire the ability to establish molecular interactions mediated by tissue-selective adhesion and chemokine receptors (homing receptors) that facilitate their access to specific organs. Recent studies have shown that an additional level of homing specificity is provided by the induction of T cell migration into the tissue by recognition of antigen displayed by the endothelium. In addition, co-stimulatory signals have been recently shown not only to regulate T cell activation and differentiation, but also to orchestrate the anatomy of the ensuing T cell response. Similarly, the characterization of migratory patterns by regulatory T cells has been the subject of many recent studies. Here, we provide an overview of key concepts, which have contribute to unraveling the complex anatomy of T cell immunity.