Cardiovascular disease (CVD) is the most frequent and costly complication of type 2 diabetes. In this review, we examine the impact of diabetes on CVD. Shedding some light on the diabetes/CVD relationship are epidemiologic studies, which focused on Native Americans, who collectively experienced little or no diabetes or CVD in the past, but experience both conditions in epidemic proportions today. Almost half of the Native Americans studied had diabetes at baseline. When CVD events were stratified by diabetic status, the relative CVD risk among diabetic men was twice that of nondiabetic men, and the risk among diabetic women was threefold that of nondiabetic women. Among all CVD events, diabetes accounted for 56% in men and 78% in women; most CVD deaths occurred in those with diabetes. Recent attention has focused on defining the relative strength of CVD risk factors in diabetic populations. In many populations, low-density lipoprotein (LDL) cholesterol is lower in diabetic individuals. However, in American Indians, every 10-mg/dL increase in LDL cholesterol has been associated with a 12% increase in CVD risk and every 10-mg/dL decrease in high-density lipoprotein (HDL) cholesterol was associated with an 8% increase in CVD risk. Albuminuria is an important predictor of CVD in diabetic populations. Those with macroalbuminuria had a CVD risk that was four to five times that of diabetic individuals without albuminuria. Other CVD risk factors in diabetes that have come under recent scrutiny in other populations are increased levels of fibrinogin, and C-reactive protein, and leukocytosis. Angiogenic response may be lower in diabetic individuals, and the possible role of infection is being examined in diabetic patients. LDL cholesterol and albuminuria should be the targets of preventive strategies, and promising new areas such as cytokines, growth factor, and the role of infection should be further explored.