In the past decade, several types of regulatory T cells (Tregs) have been identified to play a pivotal role in the control of autoimmunity and transplantation tolerance in rodents and in human beings, including innate regulatory NKT cells and gammadelta T cells, naturally occurring FoxP3 expressing CD4(+)CD25(+) T cells, and in-vitro induced Tregs including interleuking-10 (IL-10)-secreting Tr1 CD4(+) T cells, TGF-beta-producing Th3 CD4(+) T cells, anergic CD4(+) T cells, CD8(+)CD28(-) and CD3(+)CD4(-)CD8(-) T cells. Recent studies have shown that innate and adaptive Tregs may be linked and act in concert to mediate immunosuppression. As our understanding of regulatory T cell populations has substantially advanced, compelling evidence support the prospect that in-vitro expanded, patient-tailored Tregs with indirect anti-donor allospecificity could be potential reagents as adoptive cell therapy for individualized medicine to promote clinical transplantation tolerance.