Hyperglycemia and insulin resistance are independent risk factors for cardiovascular disease (CVD). Postprandial glycemic "spikes" adversely affect vascular structure and function via multiple mechanisms including oxidative stress, inflammation, low-density lipoprotein oxidation, protein glycation, and procoagulant activity. Glycemic responses can be reliably predicted by considering both the quantity and quality of carbohydrate. The glycemic index (GI), a measure of carbohydrate quality, has provided insights that knowledge of the sugar or starch content has not. In prospective observational studies, dietary GI and/or glycemic load (GL; the product of the amount of carbohydrate and GI) independently predict CVD, with relative risk ratios of 1.2 to 1.9 comparing highest and lowest quartiles. In randomized controlled trials in overweight subjects, diets based on low GI carbohydrates have decreased plasminogen activator inhibitor-1 activity and other CVD risk factors over and above that of conventional low-fat diets. Taken together, the findings suggest that clinicians may be able to improve CVD outcomes by recommending the judicious use of low GI/GL foods.