High glycemic index (GI) and glycemic load (GL) have been proposed to be associated with increased risk of lifestyle diseases. Since protein intake varies little in humans, adherence to the common recommendation to reduce fat intake probably leads to increases in carbohydrate intake, which emphasizes the need to investigate the effects of carbohydrate on diet-related conditions and diseases. This review examines the epidemiological literature linking GI and GL to heart disease, insulin sensitivity, type 2 diabetes, dyslipidemia, and obesity among initially healthy people. The evidence for associations between GI and particularly GL and health among free-living populations is mixed. Only the positive association between GI and development of type 2 diabetes was consistent across cross-sectional and longitudinal studies for both sexes. Low GI/GL may protect against heart disease in women, and cross-sectional studies indicate low GI/GL may reduce high-density-lipoprotein cholesterol and triacylglycerol levels in both sexes. Based on the evidence found in this review, it seems premature to include GI/GL in dietary recommendations.