The mechanism of maternal immunotolerance of the semiallogeneic fetus has been a matter of intense investigation. The tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) is reported to be critically implicated. This article discusses findings pertaining to the role of IDO in pregnancy, its location at the feto-maternal interface, systemic induction of IDO in pregnancy and the association of IDO to spontaneous abortion and preeclampsia. Whereas there is a large body of evidence supporting the relevance of IDO as a key immunoregulatory factor in feto-maternal tolerance, open questions remain concerning as to its role.