The collective advances made by many groups have significantly improved the results of pancreas transplantation. We have focused on the development of safe and effective immunotherapy, including a new protocol of rapid withdrawal of corticosteroids, the analysis of surgical technique of pancreas exocrine drainage on outcome and the role of SPK transplantation in patients with significant cardiovascular disease. We have found that multimodal immunotherapy including induction with tacrolimus-based maintenance combined with either MMF or sirolimus, with or without corticosteroids, resulted in excellent patient and graft survival rates with low rates of rejection. In this setting, enteric drainage was preferable to bladder drainage because of a lower rate of complications leading to hospital readmissions. Careful pretransplant screening for cardiovascular disease should be routinely performed for all SPK candidates. If successful coronary revascularization can be achieved, these patients can safely undergo SPK transplantation, with 5-year outcomes similar to those for recipients without coronary disease. Finally, we have observed that pancreas transplantation has an important ameliorating effect on hypertension that is independent of the method of pancreas exocrine drainage.