Recommendations arising from the traditional diet-coronary heart disease (CHD) paradigm, which focuses on effects of total and saturated fat on serum total and low-density lipoprotein cholesterol, may have failed to reduce CHD risk and inadvertently exacerbated dyslipidemia, insulin resistance, and weight gain, particularly among individuals who are older, female, sedentary, or obese. A suitable dietary paradigm must consider types and qualities of fats and carbohydrates consumed, their effects on a range of intermediary risk factors, and characteristics that may modify individual susceptibility. Based on current evidence, replacement of total, unsaturated, and even possibly saturated fats with refined, high-glycemic index carbohydrates is unlikely to reduce CHD risk and may increase risk in persons predisposed to insulin resistance. In contrast, a diet that is 1) rich in whole grains and other minimally processed carbohydrates; 2) includes moderate amounts of fats (approximately 30%–40% of total energy), particularly unsaturated fats and omega-3 polyunsaturated fats from seafood and plant sources; 3) is lower in refined grains and carbohydrates; and 4) eliminates packaged foods, baked goods, and fast foods containing trans fatty acids, will likely reduce the risk of CHD.