Pancreas transplantation has emerged as the single most effective way to achieve normal glucose homeostasis inpatients with type I insulin-dependent diabetes mellitus. Optimal immunosuppressive strategies for pancreas transplantation continue to evolve with the use of newer, more potent immunosuppressive agents,particularly tacrolimus, mycophenolate mofetil, and rapamycin. These agents have contributed to substantially lower rates of allograft rejection and improved graft survival. Regimens designed to avoid nephrotoxicity or spare corticosteroid therapy are emerging as the variety of drug options grows. Also contributing to progressively better results for solitary pancreas transplants are reductions in early graft loss rates and the development of safe, effective biopsy techniques, permitting accurate diagnosis of rejection. Collectively,these factors have allowed solitary pancreas allograft recipients, a group of patients with historically poor long-term graft survival, to enjoy successes nearly equivalent to those of combined kidney-pancreas transplants. Consequently, the American Diabetes Association strongly endorses pancreas transplantation in diabetic patients who have received prior kidney transplants and who have life-threatening metabolic lability.