Comprehensive very-low-calorie diet (VLCD) programs are the preferred treatment for selected obese individuals. They combine energy intakes of 400-800 kcal/day with medical monitoring and intensive lifestyle education. Typical VLCD patients have median body mass indexes of 36 kg/m2 and have median ages of 40 years. About 70% are female. Commonly associated medical problems include hypertension in 50%, hyperlipidemia in 41%, and diabetes mellitus or glucose intolerance in 14%. Typical weight loss with VLCD is around 21 kg in 16 wk. Reductions of 8-13% in blood pressure, 5-15% in serum total cholesterol, 5-20% in low-density lipoprotein-cholesterol, 15-50% in triglycerides, and decreases in blood glucose and glycohemoglobin in diabetic individuals accompany weight loss. VLCD-associated side effects can be managed medically without discontinuing treatment. Lifestyle education promotes long-term weight maintenance of approximately 56% 2 yr after VLCD treatment. Weight losses using comprehensive VLCDs allow moderately to morbidly obese persons to achieve greater benefits than other nonsurgical treatments and should be considered before opting for surgical treatment.