Although intensified insulin therapy regimens enable normalization of blood glucose levels and related metabolic parameters, these regimens are associated with an increased incidence of hypoglycemic episodes. Pancreas transplantation has achieved the goal of providing insulin independence with stable and continuous normoglycemia. But because of the associated morbidity and mortality and the need for life-long immunosuppression after transplant, it is difficult to justify pancreas transplantation in diabetic patients at a pre-uremic stage. Pancreas transplantation is therefore performed in conjugation with renal transplantation. The majority of renal transplant centers, however, have been reluctant to perform simultaneous kidney-pancreas transplantation in insulin-dependent uremic patients because of the additional risks associated with pancreas transplantation. More recently, refinements in surgical technique, introduction of new immunosuppressive agents, and better selection of transplant candidates have contributed to improved survival. Today, combined pancreas-kidney transplantation is an accepted treatment for carefully selected patients with insulin dependent diabetes and end-stage renal disease and in a small group of patients with uncontrolled severe metabolic problems. The effect of a euglycemic state after pancreas transplantation on the progression of micro- and macroangiopathy remains to be proved, although recently there is evidence to suggest that some end-organ lesions may be halted or even ameliorated. Further improvement in anti-rejection strategies may achieve better long-term graft survival and provide the incentive to perform pancreas transplantation at an earlier stage, before severe secondary complications of diabetes develop.