Sibutramine has a dual mode of action. It reduces food intake and attenuates the fall in metabolic rate associated with weight loss. The drug's neurochemical actions can also be distinguished from those of previous centrally acting anti-obesity agents. Clinical trials show that two out of three patients taking sibutramine lose >/= 5% weight and that the drug can enhance the maintenance of weight loss. Early weight loss predicts long-term success and can be used to guide clinical practice. To maximize the benefits of sibutramine, it is important that patients receive adjunctive diet and lifestyle therapy.