Atherosclerosis is the most common complication of diabetes. Epidemiologic and pathophysiologic evidence suggest a number of possible reasons for this. They include alterations in lipoproteins, platelets, soluble clotting factors, the balance of prostacyclin-thromboxane, blood pressure regulation, and arterial smooth muscle cell metabolism and proliferation. Many of these alterations may accompany hyperinsulinemia and may account for the recent evidence that hyperinsulinemia is a risk factor for atherosclerosis. Advances in this area will require the recognition that neither diabetes nor atherosclerosis are single disorders. Furthermore, new approaches are needed to study these disorders in which there may be many years of very subtle changes before any end point is apparent.