Compelling evidence suggests that diverse types of immune reactions can be suppressed by CD25+ CD4+ regulatory T cells (Tregs). Although increasing knowledge has accumulated concerning the generation and functional properties of Tregs, relatively little attention has been paid to another key question: where does immune regulation by Tregs take place in vivo? Tregs can inhibit both the priming and the effector phase of an immune response, so suppression might occur both within lymphoid tissues and at peripheral sites during immune reactions. This leads to the hypothesis that appropriate localization is indispensable for in vivo Treg function and that the migratory behavior of Treg subsets influences their in vivo suppressive capacity. Current data suggest a division of labor between subpopulations of Tregs, which is mainly based on specialized homing patterns.