Obesity is the main cause of premature death in the UK and worldwide its prevalence is accelerating rapidly. Our understanding of the physiological systems that regulate food intake and body weight has increased immensely over the past decade. Weight regulation in individuals depends on energy intake (in the form of food) and energy expenditure. It has previously been established that the hypothalamic arcuate nucleus receives appetite input signals from both the brain stem and the peripheral circulation to regulate energy homeostasis. Two types of neurone control food intake: an inhibitory neurone secreting alpha melanocyte-stimulating hormone (MSH) and cocaine and amphetamine-regulated transcript (CART) and a stimulatory neurone secreting neuropeptide Y (NPY) and agouti-regulated protein (AGRP). It was established that leptin activated the inhibitory neurone and inhibited the appetite stimulating neurone. The intestinal hormone, peptide YY (PYY), released after food ingestion acted in a similar way. In contrast the hormone of hunger ghrelin, released from the stomach in the fasting state, stimulated the appetite stimulating neurones and inhibits the appetite inhibitory neurones i.e. acts in an opposite direction. We have now identified two further gut hormones that influence appetite, oxyntomodulin and pancreatic polypeptide. Oxyntomodulin is released after food intake in a similar way to PYY and has a similar action on appetite. It belongs to the same family of peptides as glucagons-like peptide-1 (GLP-1), which was previously shown to inhibit appetite. GLP-1, however, also releases insulin (thereby causing hypoglycaemia) and has an affect on both gastric emptying rate and glucagon release. Pancreatic polypeptide (PP) belongs to the same family as NPY and PYY and is released from the PP cells in the islets of Langerhans, again after food ingestion and in parallel with insulin. Together these gut hormones form an integrated appetite regulatory system that tells the brain when the gut is empty and when it is full and regulates meal size. Of considerable interest is the finding that in obesity, the release of these hormones is altered and at least some of these changes tend to perpetuate the obesity and may thus provide clinically useful targets for pharmaceutical correction.