Intestinal transplantation has become the treatment of choice for patients who are experiencing life-threatening complications of intestinal failure. Early attempts with intestinal transplantation were unsuccessful as a consequence of both technical and immunologic failures. The introduction of tacrolimus provided the immunologic foundation needed for the field to advance. Guidelines for patient selection combined with standardization of operative procedures and postoperative management has allowed for improved patient and graft survival. There has been a gradual improvement in patient survival over the past 10 years, most notably in the past 3 years. Nutritional autonomy has been achieved in hundreds of patients worldwide. Further advancements in the understanding of the immune response to the transplanted intestine are still needed and will allow the use of new antirejection medications, resulting in improved outcomes.