The intestine has long been considered as a "forbidden" organ to transplant [Ann. Surg. 216 (1992) 223-33]. This is due to the particularly challenging nature of the immunological conflict that an intestinal graft may cause: a particularly vigorous rejection response, in addition to the capacity to mount a graft-versus-host disease (GVHD) [Transplantation 37 (1984) 429]. Currently, the short-term success of intestinal transplantation (Itx) depends upon the chronic delivery of profound immunosuppression but this causes infection, malignancies--in particular posttransplant lymphoproliferative disorder (PTLD)--and direct drug toxicity. For these reasons, the results of Itx remain inferior to those of other solid organ transplants in the middle and in the long term (Intestinal Transplant Registry: www.small-bowel-transplant.org). Improved results and wider application of Itx requires the development of protocols that would facilitate acceptance of the new intestine thereby allowing to reduce the need for immunosuppression with its attending complications. Relevant experimental data and the recent evolution in the clinical strategies used to promote acceptance of intestinal grafts are reviewed.