Small bowel transplantation is generally reserved for patients with life-threatening complications related to the administration of parenteral nutrition, which includes multiple venous thromboses impeding the placement of feeding catheters and progressive liver disease. Approximately two thirds of recipients are children, who are especially at risk of hepatic complications related to parenteral nutrition. Many patients are in poor condition preoperatively according to the Intestinal Transplant Registry (available at: http://www.intestinaltransplantregistry@uhn.on.ca), with 51% chronically hospitalized and up to 50% dying before donor organs can be provided. The main causes of graft loss are related to the complex surgery undertaken (combined liver and bowel transplants may be complicated by bile leaks or obstruction and small bowel perforation) and the necessity to treat patients with high dose immune suppression because of the highly immunogenic nature of small bowel allografts. Even so, uncontrolled rejection was reason for graft removal in 57% of cases (and death in 9%), but the main cause of death after small bowel transplantation is infection (56.1%). Fatal infectious episodes ensue from common respiratory pathogens such as parainfluenzae, intestinal viruses such as adenovirus and opportunistic pathogens such as vancomycin resistant enterococcus, pneumocystic carinii and Epstein-Barr virus. Lymphoma caused by Epstein-Barr virus is a particular risk in pediatric recipients who are usually naive to the virus, and up to 50% of infants can become infected by the graft at the time of transplant or shortly after being discharged. Treatment toxicity also contributes to mortality after transplantation: tacrolimus, mycophenolate, and sirolimus can all produce profound bone marrow suppression; nephrotoxicity also complicates the use of tacrolimus, and impaired wound healing is associated with steroids and sirolimus. New strategies are being developed to reduce the mortality after small bowel transplantation, including the use of interleukin-2 inhibitors, early detection and treatment of viruses such as Epstein-Barr virus and adenovirus, monitoring the immune responsiveness of patients, and technical improvements to the transplant operation.