Because of the overweight/obesity epidemic and attendant increase in risk of chronic disease worldwide, there is a pressing need to identify effective weight loss strategies. Current recommendations for weight loss advocate a reduced-calorie dietary pattern (lower in total fat) in conjunction with regular physical activity and behavior change. This combined approach is important for long-term adherence and weight maintenance. Several large-scale clinical trials implementing different reduced-calorie dietary patterns have shown that 4 to 10 kg of weight is typically lost. The different hypocaloric dietary patterns shown to be effective include reduced-fat diets (10%-30% of calories from fat), a Mediterranean-style diet, and diets that are reduced in energy density. The weight loss achieved is accompanied by beneficial changes in cardiovascular disease risk, including the lipid and lipoprotein profile and blood pressure. This article summarizes our current understanding of effective weight loss programs.