Diabetes mellitus is a chronic disease often leading to microvascular and macrovascular complications. There is evidence that better glycemic control by intensive insulin treatment effectively delays onset and slows the progression of diabetic complications. Despite great investigations and improvements in islet transplantation, long-term insulin independence has not been achieved in the majority of patients. Currently the only reliable option for establishing durable normoglycemia in patients with type 1 diabetes mellitus is whole pancreas transplantation. Simultaneous pancreas-kidney transplantation (SPK) has become the therapy of choice for patients with end-stage renal disease and type 1 diabetes mellitus. Over the past 20 years, outcomes of SPK have improved significantly to the point that the majority of recent data demonstrate long-term survival benefits and some protection from progressing secondary complications.