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Forkhead box P3 (FOXP3)⁺ regulatory T (T_Reg) cells are potent mediators of dominant self tolerance in the periphery. But confusion as to the identity, stability and suppressive function of human T_Reg cells has, to date, impeded the general therapeutic use of these cells. Recent studies have suggested that human T_Reg cells are functionally and phenotypically diverse. Here we discuss recent findings regarding human T_Reg cells, including the ontogeny and development of T_Reg cell subsets that have naive or memory phenotypes, the unique mechanisms of suppression mediated by T_Reg cell subsets and factors that regulate T_Reg cell lineage commitment. We discuss future studies that are needed for the successful therapeutic use of human T_Reg cells.