Several dietary approaches have reduced cardiovascular events in randomized clinical trials. Replacing saturated fat with polyunsaturated fat prevented coronary events in men, and a Mediterranean diet and fatty fish improved survival. None of these trials had much impact on total fat intake but rather increased vegetable oils, n-3 fatty acids, or many other plant foods or nutrients that are linked to coronary prevention. The reductions in cardiovascular disease (CVD) caused by these dietary therapies compare favorably with drug treatments for hyperlipidemia and hypertension. Improvement in blood lipid risk factors is an important mechanism to explain the results of trials of unsaturated fats. When saturated or trans unsaturated fats are replaced with monounsaturated or n-6 polyunsaturated fats from vegetable oils, primarily low-density lipoprotein (LDL) cholesterol decreases. The LDL to high-density lipoprotein (HDL) cholesterol ratio decreases. When carbohydrates are used to replace saturated fats, in a low-fat diet, LDL and HDL decrease similarly, and the ratio is not improved; triglycerides increase as well when carbohydrate increases, except when low glycemic index foods are used. The n-3 polyunsaturated fats in fish oils suppress cardiac arrhythmias and reduce triglycerides, but they have little effect on LDL or HDL cholesterol levels. The theme should be that diet has benefits that come directly from foods, as well as from the reduction in saturated fats, cholesterol, meats, and fatty dairy foods. It is likely that many diets could be designed that could prevent CVD. This potential diversity is crucial for engaging the diverse cultures and tastes of people worldwide in cardiovascular disease prevention.