The discovery of T regulatory cells has been one of the most important advances in basic immunology and has opened the door to the development of innovative therapeutic strategies for improving the outcome of solid organ and hematopoietic stem cell transplantation. Basic immunology is rapidly elucidating the complex biology of these cells even though the difficulties in purifying or even expanding them in vitro represent a major limitation to the development of clinical studies. The clinical benefit potentially associated with this therapeutic approach remains to be demonstrated. Meanwhile, several drugs used for the treatment of hematologic malignancies or for other purposes have been shown to upregulate the number and function of Tregs in vivo. In the near future, both ex vivo or in vivo expanded T cells are likely to enter the therapeutic armamentarium of clinical transplantation.