Currently available drugs used to treat obesity exert their main action on energy balance either by reducing energy intake or by inhibiting intestinal fat absorption. However, some ofthe drugs that reduce food intake also possess thermogenic properties that contribute to their clinical efficacy in terms ofloss of body fat and ofweight maintenance. A number of other compounds possess thermogenic effects but are used for indications other than obesity. Specific thermogenic agents developed for the treatment of obesity and diabetes are in the first phases of clinical development. Compounds are reviewed in this chapter irrespective of whether they are approved for use in obesity treatment by the U.S. Food and Drug Administration (FDA), the European CPMC, or by other regulatory bodies.