Obesity is a chronic problem affecting an increasing number of people worldwide and is now recognized as a global epidemic. Various factors involved in the complex genetic-environmental interactions that cause obesity will promote long-term positive energy balance. A cluster of environmental factors, including high energy intakes in the diet, low energy expenditure, and disturbed substrate oxidation, favour the increase and unfavourable distribution of fat mass. Obesity is a major risk factor for hypertension, cardiovascular disease development and diabetes mellitus, and represents a growing worldwide health problem. Several epidemiological studies have shown a high prevalence of cardiovascular complications and mortality in obesity and metabolic syndrome, type-2 diabetes or hypertension. For at “risk populations” predisposed to target organ damage, stringent targets for blood pressure control, dyslipidaemia, and glycaemia have been set in clinical guidelines, however clinical trial and real-life evidence suggest that these targets are difficult to achieve and sustain. The first line treatment for obesity, and obesity related conditions is weight loss. Life-style modification including low caloric diet, reducing sedentary behaviour and increasing exercise form the basis of all therapy, with more severe obesity pharmacotherapy or bariatric (weight loss) surgery may be indicated. Maintaining weight loss is often the greatest challenge. We review the effect of weight loss, using life-style modifications or bariatric surgery in obese subjects, on obesity-related hypertension, the metabolic syndrome, and some of the putative neurohormonal changes that drive obesity related disease.