Diabetes mellitus (DM) represents an enormous health care concern for the United States and other countries. According to the American Diabetes Association in 2007, there were more than 23 million Americans living with diabetes. This is a 13.5% increase from 2005, likely representing increases in Type II DM (DMII). Diabetes mellitus results when the beta cells of the pancreas are unable to produce sufficient insulin to prevent hyperglycemia. Simultaneous pancreas and kidney transplantation, or SPK, may be indicated for patients that have experienced renal failure as a complication of DM (either type I or type II). Until recently, technical failure represented a significant impediment to the success of pancreas transplantation. At the turn of the century, however, both renal and pancreatic graft survival dramatically improved. Immunologic and nonimmunologic causes of graft failure continue to challenge inpatient and outpatient management. With vigilance in the ICU postoperatively and in the clinic, SPK can provide significant benefit both in patient survival and quality of life.