Glycemic control via the use of exogenous insulin injections in diabetic patients is incomplete, resulting in multiple long-term complications, such as retinopathy, neuropathy, vasculopathy, and nephropathy. The goal of whole-pancreas and kidney transplantation is to achieve long-term insulin independence and correct uremia. The proposed benefits of pancreas and kidney transplantation are improved quality of life, prevention of recurrent diabetic nephropathy, freedom from exogenous insulin, stabilization or improvement in secondary complications, and improved mortality. No other regimen of insulin delivery or renal replacement besides pancreas and kidney transplantation can achieve this level of physiologic regulation. Copyright (C) 2011 S. Karger AG, Basel