Induction of donor-antigen-specific immunological tolerance still remains the "holy grail" in organ transplantation. Recently, Indoleamine-2,3 Dioxygenase (IDO)--a tryptophan degrading enzyme--has been shown to be implicated in one of nature's most impressive examples of tolerance, which is maternal acceptance of the semi-allogeneic foetus. Although many experimental findings propose IDO as a key player in induction and maintenance of peripheral tolerance, scepticism exists as to whether IDO represents a promising therapeutic target with clinical relevance. In this review article we will discuss the role of IDO in transplantation and take a critical look at IDO-based therapeutic strategies.