Insulin resistance is a prime risk factor associated with atherosclerosis and thrombosis. Other risk factors include dyslipidemia, obesity, and hypertension. The constellation of those factors, which is known as the cardiovascular dysmetabolic syndrome, increases the risk of macrovascular disease. Insulin resistance may contribute directly to cardiovascular disease and may also act as a precursor of diabetes, which is also associated with an increased risk of macrovascular disease. Insulin resistance can be difficult to assess clinically, but it is invariably present in patients with type 2 diabetes, impaired fasting glucose, or impaired glucose tolerance. Treatment of insulin resistance includes diet, exercise, smoking cessation, strict control of hypertension, aggressive treatment of lipid abnormalities, and keeping the hemoglobin A1c level below 7%. New oral agents improve glycemic control for those with diabetes or insulin resistance, but their role in reducing the risk of macrovascular disease is undetermined.