Patient survival after acute myocardial infarction (AMI) has improved considerably during the last several decades as percutaneous coronary intervention (PCI), fibrinolytic therapy, and other advances have entered clinical practice. Despite these improvements, the likelihood of death soon after AMI remains much greater among individuals with diabetes than among nondiabetic patients. It was long believed that the relationship between diabetes and heart disease could be explained by risk factors common to the 2 conditions. However, a number of studies have shown that hyperglycemia is directly associated with worse clinical outcomes after AMI, even after controlling for other clinical factors that are associated with diabetes. 1,2 Among nondiabetic patients, hyperglycemia at the time of AMI is associated with a high likelihood of death or heart failure, even when myocardial infarct sizes are relatively small. Acute hyperglycemia is also a significant predictor of long-term mortality after AMI. Several studies have demonstrated that there are abnormalities of myocardial blood flow in patients with diabetes and that hyperglycemia is associated with impairments of myocardial blood flow before and after PCI. Clinical studies that have investigated the therapeutic potential of insulin treatment in patients with AMI have produced conflicting results. In the Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI) trial, insulin infusion improved clinical outcomes after AMI in patients with diabetes, especially among those with the highest baseline blood glucose levels. In the recent Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment E American Study Group (CREATE-ECLA), an infusion of a glucose-insulin-potassium (GIK) solution did not significantly improve clinical outcomes after AMI, although the treatment regimen used produced a significant increase in plasma glucose level from baseline soon after admission. The true benefit of insulin therapy for AMI and the best ways to incorporate insulin treatment into current treatment strategies require additional study.