The obesity epidemic is now widely recognized as a major threat to health in many different countries. Some surgical therapies for obesity are efficacious and indicate that signals from the gastrointestinal tract are capable of exerting beneficial long-term effects on food intake and body weight. The development of non-surgical therapies targeting this system depends on understanding how food, and the absence of food, in the gastrointestinal tract signals to those parts of the brain that regulate feeding behaviour. What can be called gastrointestinal surveillance systems include both nervous pathways linking the gut and brain, and some gut hormones. Nutrient sensing mechanisms within the gastrointestinal tract determine the release of satiety hormones such as cholecystokinin (CCK), or appetite stimulating hormones such as ghrelin, and offer potential therapeutic targets. It seems that CCK and ghrelin both act on the vagus nerve that links the gut to the brain. Examples of interactions between different factors regulating this pathway are discussed. It is argued that sufficient is now known to indicate that this signalling system can provide new targets for the treatment of obesity.