Diabetic patients have a threefold higher risk of developing atherosclerosis and its clinical complications compared with nondiabetic individuals. Part of the cardiovascular risk associated with diabetes is probably due to genetic determinants influencing both glucose homeostasis and the development of atherosclerosis. However, type 2 diabetes frequently coexists with other cardiovascular risk factors such as arterial hypertension, central obesity, and dyslipidemia. Genetic variability affects many areas, such as lipid and energy metabolisms, hypertension and hemodynamic mechanisms, blood clotting homeostasis, inflammation, and matrix turnover in the vascular wall, and will have an impact on the development of macrovascular complications in diabetic patients. These individual susceptibility factors each contribute only a small increased risk interacting with environmental determinants.