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Several decades of epidemiological and clinical research have identified physical inactivity, excessive calorie consumption, and excess weight as common risk factors for both type 2 diabetes mellitus and coronary heart disease. This trio forms the environmental substrate for a now well-recognized metabolic phenotype called the insulin resistance syndrome. Recent data suggest that a high intake of rapidly absorbed carbohydrates, which is characterized by a high glycemic load (a measure of carbohydrate quality and quantity), may increase the risk of coronary heart disease by aggravating glucose intolerance and dyslipidemia. These data also suggest that individuals who are obese and insulin resistant are particularly prone to the adverse effects of a high dietary glycemic load. In addition, data continue to accumulate suggesting the important beneficial effects of physical activity, even at moderate levels, and weight reduction on improving insulin sensitivity and reducing the risk of coronary heart disease. Future metabolic studies should continue to quantify the physiological impact of different foods on serum glucose and insulin, and such information should routinely be incorporated into large-scale and long-term prospective studies, in which the possible interaction effects between diet and other metabolic determinants such as physical activity and obesity can be examined. Until more definitive data are available, replacing refined grain products and potatoes with minimally processed plant-based foods such as whole grains, fruits, and vegetables, and reducing the intake of high glycemic load beverages may offer a simple strategy for reducing the incidence of coronary heart disease.