Foxp3(+)CD4(+) T cells represent a population of naturally arising suppressor T cells that are crucial for the control of autoimmune responses. The suppressive activity of this T cell subset relies on multiple mechanisms that include secretion of anti-inflammatory factors such as TGF-beta or IL-10. Novel studies now establish that, through the generation of the immunosuppressive factor adenosine, the ectoenzymes CD39 and CD73 are important contributors to the regulatory activity of Foxp3(+)CD4(+) T cells.