Food intake is controlled in the brain which integrates important regulatory information from the periphery, especially the gut. A large part of this gut-brain signaling is transmitted by the vagus nerve from the gastrointestinal tract to the brainstem. Mechanical as well as chemical information is sensed by vagal afferents through direct activation of mechano- and chemoreceptors triggered by peptides such as ghrelin, cholecystokinin, glucagon-like peptide-1, peptide YY and glucagon, or transmitters (serotonin) released from enteroendocrine cells. The activated vagus in turn stimulates cells in brainstem nuclei eliciting reflexes that influence feeding behavior, gut hormonet, and gastric functions such as motility as well as secretion and are involved in glucose homeostasis. Therefore, the brainstem and the vagus are actively involved in food intake and digestive processes. Obesity and associated diseases are major health problems in the industrialized countries and curative measures are limited. The most effective treatment is bariatric surgery that bypasses the stomach and may involve a vagal component underlying the sustained weight loss. Besides surgery, drugs, and cognitive approaches, gastric electrical stimulation has also been shown to induce long-lasting weight loss. However, further studies are needed to unravel the role of the vagus nerve for weight loss after those procedures and optimizing therapeutic strategies.