Irreversible intestinal failure in children is predominantly caused by surgical conditions such as volvulus, necrotizing enterocolitis, and gastroschisis. Functional intestinal failure from motility disorders such as intestinal pseudo-obstruction or enterocyte dysfunction with microvillus inclusion disease also may require intestine replacement. Approved indications for intestinal transplantation include liver dysfunction, loss of major venous access, frequent central line-related sepsis, and recurrent episodes of severe dehydration despite intravenous fluid management. Surgical options include transplantation of the isolated intestine, combined liver-intestine transplantation, or multivisceral transplantation of the stomach, duodenum, pancreas, and small bowel (with or without the liver). Immunosuppression for intestinal transplantation is based on tacrolimus therapy, often with induction immunosuppression using antilymphocyte antibodies (eg, antithymocyte antibody and alemtuzumab). Experience at centers of excellence demonstrates 1- and 5-year patient survival rates of 95% and 77%, respectively, with ongoing investigations focusing on lowering long-term causes of graft loss such as chronic rejection.