Regulatory T cells (Tregs) are critical regulators of peripheral immune tolerance. Treg insufficiency can lead to autoimmune disorders, including type 1 diabetes (T1D). Increasing evidence in mouse models of T1D, as well as other autoimmune disorders, suggests that there are defects in Treg-mediated suppression. Indeed, whereas Treg frequency in the peripheral blood of T1D patients is unaltered, their suppressive abilities are diminished compared with Tregs in healthy controls.