Patients with overweight or obesity are in need to loose weight and represent a particularly challenging medical condition. Undoubtedly, any intervention achieving a negative energy balance over an extended time period will result in weight loss. Although several treatment modalities are available, currently the most extended approaches are lifestyle changes, pharmacotherapy, and bariatric surgery. Given the limited approved anti-obesity drugs, the main therapeutic strategies involve either conventional treatment or bariatric surgery. Conventional weight-reduction programs pursue a safe weight loss rate of 0,5-1,0 kg per week. The main modifiable factors affecting energy balance are dietary energy intake and energy expended through physical activity. In spite of the difficulty in achieving relevant and sustained weight loss via the conventional approach, some patients are successful in reducing weight and obesity-associated complications. Bariatric surgery has proved to be the most effective long-term treatment for weight loss and comorbidity improvement. While some of the surgery-induced benefits are directly dependent on adipose tissue reduction, others are due to specific gastrointestinal changes that take place early on and before any significant effects on body weight are observed. The present study contemplates the determination and comparison of the anthropometric and metabolic changes produced by the conventional and surgery-induced treatment modalities. Particular emphasis will be placed on the potential differential effects between conventional and surgical weight loss on body composition changes, circulating adipokines and gastrointestinal hormones together with their subsequent impact on cardiometabolic risk factors.