To provide an overview of the published scientific information on the safety and efficacy of very low-calorie diets (VLCDs) and to provide rational recommendations for their use. Original reports obtained through a MEDLINE search for 1966 through 1992 on VLCDs or reducing diets plus obesity, supplemented by a manual search of bibliographies and the opinions of experts in the field of nutrition and weight loss therapy for obesity. Only studies of humans were cited. Current VLCDs are usually provided in the context of comprehensive treatment programs, during which usual food intake is completely replaced by specific foods or liquid formulas containing 3350 kJ/d (800 kcal/d) or less. Weight loss on VLCDs averages 1.5 to 2.5 kg/wk; total loss after 12 to 16 weeks averages 20 kg. These results are superior to standard low-calorie diets of 5020 kJ/d (1200 kcal/d), which lead to weight losses of 0.4 to 0.5 kg/wk and an average total loss of only 6 to 8 kg. There is little evidence that intakes of less than 3350 kJ/d (800 kcal/d) result in better weight losses than 3350 kJ. Intake of at least 1 g/kg of ideal body weight per day of protein of high biologic value appears to be important in helping to preserve lean body mass. Serious complications of modern VLCDs are unusual, cholelithiasis being most common. Current VLCDs are generally safe when used under proper medical supervision in moderately and severely obese patients (body mass index [weight in kilograms divided by height in meters squared] >30) and are usually effective in promoting significant short-term weight loss, with concomitant improvement in obesity-related conditions. Long-term maintenance of weight lost with VLCDs is not very satisfactory and is no better than with other forms of obesity treatment. Incorporation of behavioral therapy and physical activity in VLCD treatment programs seems to improve maintenance. © 1993, American Medical Association. All rights reserved.