This review summarizes the outcomes and known adverse effects of current immunosuppression strategies in use in pediatric intestinal transplantation. Intestinal transplantation has evolved from an experimental therapy to a highly successful treatment for children with intestinal failure who have complications with total parenteral nutrition. Because of continued success with intestinal transplantation over the past decade, the focus of clinicians and researchers is shifting from short-term patient survival to optimizing long-term outcomes. Current 5-year patient and graft survival rates after intestinal transplantation are 58% and 40%, respectively, in the US; single centers have reported nearly 80% patient and 60% graft survival rates at 5 years. The immunosuppression strategy in intestinal transplantation includes a tacrolimus-based regimen, usually in conjunction with an antibody induction therapy such as rabbit-antithymocyte globulin, interleukin-2 receptor antagonists, or alemtuzumab. The use of these immunosuppressive regimens, along with improved medical and surgical care, has contributed significantly toward improved outcomes. Optimization of post-transplant immunosuppression strategies to reduce adverse effects while minimizing acute and chronic graft rejection is a strong clinical and research focus.