Cellular therapies using regulatory T (T_reg) cells are currently undergoing clinical trials for the treatment of autoimmune diseases, transplant rejection and graft-versus-host disease. In this Review, we discuss the biology of T_reg cells and describe new efforts in T_reg cell engineering to enhance specificity, stability, functional activity and delivery. Finally, we envision that the success of T_reg cell therapy in autoimmunity and transplantation will encourage the clinical use of adoptive T_reg cell therapy for non-immune diseases, such as neurological disorders and tissue repair.