The prevalence of obesity has increased to epidemic proportions and has become an urgent public health problem. Obesity causes significant morbidity and mortality and its impact on health-care costs in the United States is growing dramatically. Apart from bariatric surgery treatment, options are limited. Future advances in treatment will rely on a better understanding of the pathogenesis and physiology of obesity. Alterations in gastrointestinal (GI) sensory-motor function and symptoms have been associated with obesity. GI neuroendocrine communications between the periphery and the brain regulate energy balance and ingestive behaviors. These interactions are largely mediated by the gut-brain peptides through negative and positive feedback loops that maintain energy homeostasis. Bariatric surgery has been shown effective, but the mechanisms of weight loss following these procedures clearly require further studies and a better understanding of the affects of bariatric surgery on the gut-brain neuropeptide homeostasis. Gut-brain peptides may provide attractive therapeutic targets in the fight against this very morbid disease. We review alterations in GI function and some of the more important gut-brain neuropeptides that occur in obesity.