This review aims to give a brief overview of NPY receptor distribution and physiology in the brain and summarizes series of studies, test by test and region by region, aimed at identification receptor subtypes and neuronal circuitry mediating anxiolytic-like effects of NPY. We conclude that from four known NPY receptor subtypes in the rat (Y 1 , Y 2 , Y 4 , Y 5 ), only the NPY Y 1 receptor can be linked to anxiety-regulation with certainty in the forebrain, and that NPY Y 2 receptor may have a role in the pons. Microinjection studies with NPY and NPY receptor antagonists support the hypothesis that the amygdala, the dorsal periaqueductal gray matter, dorsocaudal lateral septum and locus coeruleus form a neuroanatomical substrate that mediates anxiolytic-like effects of NPY. The release of NPY in these areas is likely phasic, as NPY receptor antagonists are silent on their own. However, constant NPY-ergic tone seems to exist in the dorsal periaqueductal gray, the only brain region where NPY Y 1 receptor antagonists had anxiogenic-like effects. We conclude that endogenous NPY has an important role in reducing anxiety and serves as a physiological stabilizer of neural activity in circuits involved in the regulation of arousal and anxiety.