Orlistat (tetrahydrolipstatin) is an inhibitor of gastrointestinal lipases, especially pancreatic lipase. It is used as an adjunct to diet and exercise in order to achieve weight loss in obese individuals (body mass index > 30 kg/m2) or in overweight individuals (body mass index > 27 kg/m2) with other risk factors for atherosclerotic vascular disease, such as hypertension, dyslipidaemia or diabetes. Short- and long-term studies of up to 4 years duration have shown the drug to have significant benefits in weight loss, as well as in the reduction in lipids, glucose and haemoglobin A1c, and in time to onset of Type 2 diabetes compared with diet alone or placebo groups. The incremental amount of weight loss that orlistat produces is modest, but sufficient to result in improvement in obesity comorbidities such as elevated blood pressure, dyslipidaemia and hyperglycaemia compared with diet and exercise alone. Orlistat should only be prescribed for individuals who are motivated to adhere to lifestyle modifications, especially dietary fat restriction.