Intestinal failure can be treated with bowel rehabilitation, total parenteral nutrition, or intestinal transplantation. Little has been done to integrate these therapies for patients with intestinal insufficiency or failure and to develop an algorithm for appropriate use and timing. We established a multidisciplinary program using bowel rehabilitation, total parenteral nutrition, or intestinal transplantation as appropriate in a large population. Evaluation included clinical, pathologic, and psychosocial assessments and assignment to therapy based on the results of this evaluation. Of 59 patients evaluated for life-threatening complications of intestinal failure, 68% were considered appropriate candidates for transplantation, 10% were managed with rehabilitation, and 17% were maintained on optimized long-term parenteral nutrition. Nineteen transplants were performed, with 78% patient survival and 66% graft survival. Patient survival among isolated intestine recipients was 90%. All patients managed with rehabilitation were weaned from parenteral nutrition within 6 months. Long-term management with parenteral nutrition resulted in a significant number of deaths both among patients waiting for a transplant and those who were poor candidates for transplant. Intestinal rehabilitation, when successful, is optimal. For patients with irreversible intestinal failure, isolated intestinal transplantation holds particular promise. Parenteral nutrition is plagued by high failure rates among this population of debilitated patients compared with the general parenteral nutrition population. Integration of these therapies, with individualization of care based on a multidisciplinary approach and perhaps with earlier isolated intestinal transplantation for patients with irreversible intestinal failure, should optimize survival.