Many peptides are synthesized and released from the gastrointestinal tract. Although their roles in the regulation of gastrointestinal function have been known for some time, it is now evident that they also physiologically influence eating behavior. Our understanding of how neurohormonal gut-brain signaling regulates energy homeostasis has advanced significantly in recent years. Ghrelin is an orexigenic peptide produced by the stomach, which appears to act as a meal initiator. Satiety signals derived from the intestine and pancreas include peptide YY, pancreatic polypeptide, glucagon-like peptide 1, oxyntomodulin, and cholecystokinin. Recent research suggests that gut hormones can be manipulated to regulate energy balance in humans, and that obese subjects retain sensitivity to the actions of gut hormones. Gut hormone-based therapies may thus provide an effective and well-tolerated treatment for obesity.