There is at present a justifiable debate as to the optimum level of total dietary fat which will reduce the risk of obesity without an elevation of plasma triacylglycerol or a depression of plasma HDL-cholesterol. Total plasma cholesterol and LDL-cholesterol levels are lowered and risk of fatal myocardial infarction is lowered when either saturated or trans-unsaturated fatty acids are replaced isoenergetically by either monounsaturated or polyunsaturated fatty acids. The triacylglycerol-raising and HDL-lowering effects of low-fat high-carbohydrate diets can be over-come with low intakes of n−3 polyunsaturated fatty acids and moderate exercise. Whilst a reduction in dietary fat is being attained in many countries, the reduction is uniform across all fatty acids, leaving dietary fat composition unchanged. The ability of low-fat diets to reduce cholesterol and cause a fall in body weight is not influenced by the carbohydrate ratio starch: sugars in the diet. However, weight-gain susceptibility to high intakes of dietary fat and the plasma cholesterol responsiveness to diet are considerably influenced by common genetic polymorphisms.