Hyperglycemia and hyperinsulinemia are central features of the metabolic syndrome and type 2 diabetes mellitus, which contribute to the pathogenesis of coronary heart disease (CHD). Recent data indicate that increased dietary glycemic load (GL) due to replacing fats with carbohydrates or increasing intake of rapidly absorbed carbohydrates (ie, high glycemic index) can create a self-perpetuating insulin resistance state and predicts greater CHD risk. In this paper, we discuss the historic development of the GI and GL concepts and summarize metabolic experiments and epidemiologic observations relating to clinical utilities of these measures. On balance, increased consumption of low-GI foods leads to improvements in glycemia and dyslipidemia in metabolic studies, and a low-GL diet has been associated with lower risk of type 2 diabetes and CHD in prospective cohort studies. We conclude that decreasing dietary GL by reducing the intake of high-glycemic beverages and replacing refined grain products and potatoes with minimally processed plant-based foods such as whole grains, fruits, and vegetables may reduce CHD incidence in sedentary individuals and populations with a high prevalence of overweight. Because of advances in food-processing technologies and changes in ingredients in our food supply, the composition and physiologic effects of foods are likely to change over time. Future efforts should continue to quantify and monitor the metabolic impacts of different foods, and such information should be routinely incorporated into long-term prospective studies to allow for the assessment of the interactive effects of diets and other metabolic determinants on chronic disease risk.