CD4(+)CD25(+) T cells were identified originally as potent suppressors of autoimmunity and were later termed "natural regulatory T cells" or nTreg cells. Subsequently, a transcription factor called forkhead box protein 3 (Foxp3) was identified to be a critical regulator for Treg differentiation and function. Foxp3(+)CD4(+)CD25(+) Treg cells have been increasingly documented to suppress allograft rejection and to mediate allograft tolerance in transplantation. In this article, the authors review current approaches for amplification of allo-specific Foxp3(+)CD4(+)CD25(+) Treg cells for prevention of allograft rejection and induction of allo-specific transplant tolerance.