The risk of ischemic heart disease is 2-4 times greater in diabetes, occurs at a younger age, and is much higher in women with diabetes. The risk of coronary disease is increased in patients with poor glycemic control, but studies have not shown a major impact of improved glucose management on cardiovascular mortality. This apparent contradiction may be due to the many potential mechanisms of increased cardiovascular damage in diabetes, including hypertension; abnormal clotting function due to changes in fibrinolysis, platelet adherence, and plasminogen activity; abnormal vascular reactivity; and abnormal lipid patterns and particles. Some, but not all, of these issues are related to lifestyle factors, including diet, exercise, and cigarette smoking. The treatment of hypertension and hypercholesterolemia has been more successful in reducing cardiovascular mortality than reducing HbA1c levels. One of the major, unresolved questions is whether insulin resistance rather than hyperglycemia is the primary risk factor for cardiovascular disease (CVD). Antidiabetic agents that target insulin resistance may be more cardioprotective than those that primarily augment insulin secretion.