Adequate food intake and body fat stores are essential for survival. As a consequence complex systems regulating feeding behaviour have developed. An increased understanding of how peripheral energy signals act upon these circuits to regulate food intake is essential for effective treatment of the current obesity crisis. In recent years it has become apparent that hormones released from the gut play crucial roles in the regulation of hunger and body weight. Peptide YY (PYY), synthesised by gut-endocrine L-cells, predominantly as an N-terminally truncated form PYY3-36, is one such hormone. Exogenous administration of PYY3-36 reduces food intake in obese humans and rodents. Moreover, new lines of evidence support a role for endogenous PYY3-36 in regulating energy homeostasis. The NPY-Y2 receptor mediates the anorectic actions of PYY3-36 with rodent studies implicating the hypothalamus, vagus and brainstem as key target sites. Functional imaging in humans has confirmed that PYY3-36 activates brainstem and hypothalamic regions. The greatest effects, however, were observed within the orbitofrontal cortex, a polymodal brain region involved in reward processing. Further evidence for a hedonic role for PYY3-36 is supported by rodent studies showing that PYY3-36 decreases the motivation to seek high-fat food. These emerging hedonic effects of PYY3-36 together with the weight-reducing effects observed in obese rodents suggest that targeting the PYY system may offer a therapeutic strategy for obesity.