Orlistat has been shown to cause meaningful and sustained weight loss in overweight or obese adults when given at a dose of 120 mg 3 times daily and combined with a mildly reduced-calorie diet for up to 4 years. Because of the nonsystemic mechanism of action of orlistat, it was considered a logical choice for study in the obese pediatric population. In the current study, the same dosage of orlistat was associated with a statistically significant decrease in BMI over the course of 1 year in contrast to a BMI increase in the placebo group. This result must be interpreted considering the characteristics of an adolescent rather than an adult population.