Type I diabetes is increasing in incidence in developed countries . Diabetes arises from a breakdown of tolerance to islet antigens, resulting in T cell-driven destruction of the islet cells and concomitant hyperglycemia. In this review, we explore whether this loss of tolerance results in part from a defect in the action of regulatory T cells. We draw on both human data and that obtained from NOD mice, the murine model of autoimmune diabetes. Although insulin-based therapies have been highly successful in treating diabetes, the complications of long-term hyperglycemia are still major causes of morbidity and mortality. Accordingly, we also discuss whether treatment with regulatory T cells is a viable method for restoring long-term tolerance to self-antigens in recently diagnosed or pre-diabetic individuals. Regulatory T cell therapy offers many potential advantages, including a specific and lasting dampening of inflammation. However, some significant hurdles would have to be overcome before it could become an established treatment.