Orlistat is an inhibitor of gastrointestinal lipases and, therefore, prevents the absorption of dietary fat. This agent reduces weight in obese adults and adolescents with or without comorbidities (including type 2 diabetes mellitus, hypercholesterolaemia, hypertension, metabolic syndrome) who received up to 4 years of therapy in conjunction with a hypocaloric diet. In obese patients, orlistat in combination with a hypocaloric diet improved metabolic risk factors and reduced the risk of developing type 2 diabetes. Furthermore, this agent was cost effective in patients with obesity, particularly those with type 2 diabetes. Orlistat is generally well tolerated, with gastrointestinal adverse events being most commonly reported. Orlistat, in addition to lifestyle and dietary intervention, is thus an attractive option for the treatment of patients with obesity, especially those with associated comorbidities or at risk of developing type 2 diabetes.