Orlistat (Xenical, Hoffmann-La Roche) is a powerful inhibitor of gastrointestinal lipase and as such, reduces fat absorption. Unlike other weight-reducing drugs it is minimally absorbed and has no effects in the CNS. Orlistat is indicated for patients with a body mass index (BMI) of at least 30 kg/m2 or 28 kg/m2 in the presence of obesity-associated complications, such as hypertension, diabetes mellitus, hyperlipidaemia and obstructive sleep apnoea. In clinical trials, orlistat (120 mg t.i.d.) in combination with life-style modification and a hypocaloric diet (30% of energy from fat) induced significantly more weight loss and improved health complications of obesity (diabetes, hypertension, hyperlipidaemia) compared to patients treated with diet alone. Side effects related to fat malabsorption, occurred in more than 20% of subjects during the first year of treatment and included oily faecal spotting, abdominal pain, flatus with discharge and fatty/oily stool. Side effects from orlistat diminished in the second year of treatment. Plasma concentrations of fat soluble vitamins decreased in orlistat-treated patients but did not usually fall below the normal range. No studies have evaluated the efficacy of orlistat or side effect profile beyond two years.