Over the last few years, weight loss has been recognised as a key factor in the control and prevention of coronary heart disease, hypertension, type 2 diabetes, hyperlipidaemia, cardiorespiratory failure and other chronic degenerative diseases. It has been shown that even a modest loss of 5% of initial body weight can reduce, eliminate or prevent these disorders in a large proportion of overweight patients. The early benefits of weight loss can be explained by the direct effects of a low calorie diet, but the long-term effects can only partially be attributed to diet, physical exercise or behavioural modifications. Long-term studies have shown that a sustained moderate weight loss of 10% improves glycemic control as a result of reduced insulin resistance, the better control or prevention of hypertension, increased HDL-and decreased LDL-cholesterol and VLDL triglycerides, improved diastolic function and the propagation of a cardiac stimulus that reduces the risk of ventricular arrhythmias. The health benefits of modest weight loss are particularly evident and useful when excess body fat is a major health hazard, as in the case of class III obesity (BMI > 40 kg/m2), which is often characterised by prevalent visceral fat accumulation. Baseline serum glucose, cholesterol, triglyceride, uric acid and blood pressure levels are usually higher in the upper body than is the case in peripheral obesity, and tend to decrease more in response to moderate weight loss. A therapeutic programme aimed at obtaining a gradual and moderate weight loss avoids the complications due to the rapid weight loss associated with inappropriate, unbalanced diets or even more harmful treatments. These complications include cholelithiasis and the subsequent risk of cholecystitis, lean body mass loss and a stable decrease in energy expenditure with a high probability of regaining weight (weight cycling syndrome). In conclusion, a large number of obese patients may be sensitive to a modest weight loss even without the achievement of ideal body weight. Sustained moderate weight loss by itself is definitely beneficial in obesity (especially "malignant" and "morbid" obesity), but also in diabetes, hypertension, hyperlipidaemia, cardiorespiratory diseases and other chronic degenerative diseases associated with any degree of excess body fat.