The first pancreas transplant in 1966 demonstrated that a pancreas allograft could reestablish euglycemia independent of exogenous insulin in patienta with type 1 diabetes mellitus. Early outcomes were poor, and application of the procedure was limited. In the 1980s, innovations in immunosuppiession therapy and surgical management of pancreatic exocrine secretions combined with careful candidate selection resulted in dramatic improvements in patient and graft survival. In the 1990s, the incorporation of additional new anti-rejection agents into immunosuppression protocols resulted in a further decrease in the incidence of acute rejection, affording more freedom in surgical management of exocrine drainage. The vision for the future of transplantation for the treatment of diabetes is focused on the percutaneous infusion of pancreatic islets, thus eliminating the need for surgical revascularization of a pancreas allograft, yet reestablishing regulation of glucose metabolism.