Dietary guidelines continue to recommend restricting intake of saturated fats. This recommendation follows largely from the observation that saturated fats can raise levels of total serum cholesterol (TC), thereby putatively increasing the risk of atherosclerotic coronary heart disease (CHD). However, TC is only modestly associated with CHD, and more important than the total level of cholesterol in the blood may be the number and size of low-density lipoprotein (LDL) particles that contain it. As for saturated fats, these fats are a diverse class of compounds; different fats may have different effects on LDL and on broader CHD risk based on the specific saturated fatty acids (SFAs) they contain. Importantly, though, people eat foods, not isolated fatty acids. Some food sources of SFAs may pose no risk for CHD or possibly even be protective. Thus, advice to reduce saturated fat in the diet without regard to such nuance could actually increase people’s risk of CHD. When saturated fats are replaced with refined carbohydrates, and specifically with added sugars (like sucrose or high fructose corn syrup), the end result is not favorable for heart health. Such replacement leads to changes in LDL, high-density lipoprotein (HDL), and triglycerides that may increase the risk of CHD. Additionally, diets high in sugar may induce many other abnormalities associated with elevated CHD risk, including elevated levels of glucose, insulin, and uric acid, impaired glucose tolerance, insulin and leptin resistance, non-alcoholic fatty liver disease, and altered platelet function. A diet high in added sugars has been found to cause a 3-fold increased risk of death due to cardiovascular disease. But sugars, like saturated fats, are a diverse class of compounds. The monosaccharide, fructose, and fructose-containing sweeteners (e.g., sucrose) result in greater degrees of metabolic abnormalities than seen with glucose (either isolated as a monomer or in chains as starch) and may present greater risk for CHD. This paper reviews the evidence linking saturated fats and sugars to CHD, and concludes that the latter is more of a problem than the former. Dietary guidelines should shift focus away from reducing saturated fat, and from replacing saturated fat with carbohydrates, specifically when these carbohydrates are refined. To reduce the burden of CHD, guidelines should focus particularly on reducing intake of concentrated sugars, specifically the fructose-containing sugars like sucrose and high-fructose corn syrup in the form of ultra-processed foods and beverages.