The optimal diet for prevention of weight gain, obesity, metabolic syndrome, and type 2 diabetes is fat-reduced, fibre-rich, high in lowenergy density carbohydrates (fruit, vegetables, and whole grain products), and intake of energy-containing drinks is restricted. The reduction of the total fat content of ad libitum diets produces weight loss in both the short-term and over periods as long as 7 years. A fat-reduced diet, combined with physical activity, reduces all risk factors for cardiovascular disease, and reduces the incidence of type 2 diabetes. The combination of reduction of dietary fat and energy, and increased physical activity, has been shown to reduce the incidence of diabetes by 58% in two major trials. In post hoc analyses the reduction in dietary fat (energy density) and increase in fibre were the strongest predictors of weight loss and diabetes protective effects. It remains to be shown whether a low-glycemic index diet provides benefits beyond this. Low-carbohydrate diets may be an option for inducing weight loss in obese patients, but a very low intake of carbohydrate-rich foods is not commensurate with a healthy and palatable diet in the long term. However, there is evidence that increasing the protein content of the diet from 15% up to 20–30%, at the expense of carbohydrate, increases the satiating effect of the diet, and induces a spontaneous weight loss, and this could turn out to be a preferred option for patients with metabolic syndrome and type 2 diabetes.