CD4⁺CD25⁺Foxp3⁺ regulatory T (Treg) cells migrate into both inflammatory sites and draining lymph nodes (LNs) during an immune response, and have unique and overlaping functions in each location. Current studies suggest that Treg cells in draining LNs and inflamatory sites may not simply be a division of labor, but rather Treg cells migrate in a coordinated fashion between peripheral tissues and draining LNs. Trafficking between inflammatory sites and draining LNs is not only crucial for Treg cells to act, but also for them to acquire optimal immune regulatory activities. Furthermore, recent work has revealed that T helper (Th)1, Th2 and Th17 cell master transcription factors control Treg cell function by regulating genes important for Treg cell migration and suppression, and consequently affect disease pathogenesis.