Since obesity is a chronic disorder, a long-term approach is essential, and modern obesity pharmacotherapy means medicating as an adjunct to diet and physical activity not only to achieve weight loss, but also to maintain it. Sibutramine is a US Food and Drug Administration- and European Committee for Proprietary Medicinal Products-approved medication with demonstrated efficacy in long-term obesity management. It is a norepinephrine-serotonin reuptake inhibitor and produces weight loss by a dual mechanism: reduction of food intake and increase in energy expenditure. Sibutramine is given once daily in doses ranging from 5-15 mg. The amount of weight lost with sibutramine is related to both the dose of the drug and the intensity of the behavioral therapy component. Sibutramine produces a weight loss from baseline of more than 5% in over 75% of patients who are prescribed 15 mg daily, and it produces weight loss that averages 5-8% from baseline, independently of the behavioral approach. Weight loss with sibutramine is associated with improvement in waist circumference, lipids, glycemic control, uric acid and health-related quality of life. Sibutramine use is associated with small increases in mean resting blood pressure, but the individual response is variable and not all patients will have blood pressure increases. The drug is also associated with small increases in mean heart rate and should therefore not be used in patients with a history of cardiac arrhythmia. Because it is a serotonin and norepinephrine reuptake inhibitor, sibutramine should not be used with monoamine oxidase inhibitors or noradrenergic agents, and caution is advised in prescribing sibutramine to patients on selective serotonin reuptake inhibitor antidepressants. Given the growing appreciation for the health benefits that can be achieved with even a relatively small weight loss, physicians must become adept in office approaches to achieve modest weight loss. Sibutramine is a useful adjunct to diet and physical activity approaches and can help selected patients achieve and maintain weight loss with concomitant health benefits.