Small bowel transplantation (SBT) would, in theory, be the treatment of choice for patients suffering from the short bowel syndrome. Although SBT has been done with a considerable degree of success in some centers [36, 145], it is by no means an established or widely applicable therapy for those with short bowel syndrome. The small bowel is unique among vascularized organ grafts because it not only elicits a vigorous rejection reaction but is also capable of inducing graft-versus-host disease (GVHD). Rejection of the graft does not only lead to loss of function but also to bacterial translocation. The risk of fatal sepsis is aggravated by the immunosuppression given to prevent rejection. Here, the history of SBT is described, and recent developments in experimental and clinical SBT, as well as future prospects for this theoretically optimal treatment modality for patients dependent on total parenteral nutrition (TPN) for life, are outlined.