Proper control of defined microenvironments requires that regulatory elements adapt but are also appropriately targeted to the site of disease. One major arm of the regulatory network is constituted by regulatory T (Treg) cells that restrain a large array of immune responses ranging from self-reactive to pathogen-specific reactions. Despite extensive studies on the role of Treg cells in the control of peripheral homeostasis, the site(s) in which these cells primarily act remains unclear. Treg cells, consistent with their central role in the preservation of tissue integrity, can accumulate at sites of inflammation or infection (Wei et al., 2006). However, in most circumstances as in the context of experimental colitis, Treg cells migrate both to the draining lymphoid organ and the inflamed site (Mottet et al., 2003). In this issue of Immunity, Zhang et al. (2009) showed that suppressive functions get upregulated on the Treg cell when they first traffic to the inflamed allograft and that this education at the diseases site is required for optimal control of responses in both the lymph node and the tissue.