Many peptides are synthesised and released from the gastrointestinal tract. Although their roles in the regulation of gastrointestinal function have been known for some time, it has become increasingly evident that they also influence eating behaviour. Peptide YY (PYY) is released postprandially from gastrointestinal L-cells with glucagon-like peptide 1 (GLP-1) and oxyntomodulin. Following peripheral administration of PYY3-36, the circulating form of PYY, to mouse, rat or human there is marked inhibition of food intake. Obese subjects have lower basal fasting PYY levels and have a smaller postprandial rise. However, obesity does not appear to be associated with resistance to PYY (as it is with leptin) and exogenous infusion of PYY3-36 results in a reduction in food intake by 30% in an obese group and 31% in a lean group at a buffet meal. Overall PYY significantly reduced 24-h caloric intake in both obese (16.5%) and lean groups (23.5%). Obesity is the current major cause of premature death in the UK, killing almost 1000 people a week. Worldwide its prevalence is accelerating. The administration of the naturally occurring gut hormone may offer a long-term therapeutic approach to weight control. Here, the therapeutic potential of PYY is considered.