Although advances have been made in the treatment of obese and overweight patients, no "magic bullet" yet exists. Future targets for pharmacotherapy include the OB protein leptin, neuropeptide, beta 3-adrenergic receptors, uncoupling proteins 2 and 3, and protein kinase A. Cholecystokinin, bombesin, and glucogen-like peptide-1, receptors for gastrointestinal hormones, offer potential future pharmacologic agents that enhance energy expenditure, and they have proven promising for the development of appetite-suppressant pharmacotherapy. Receptor agonists for each of these proteins have been shown to be useful as appetite suppressants and reducing meal size. This article discusses various research modalities currently under consideration. Despite rapid strides toward an ideal antiobesity agent, the role of diet, exercise, and behavior modification must be considered the cornerstone for any potential future pharmacotherapy.