In recent years, evidence has emerged suggesting that neuropeptide Y (NPY) is involved with neurobiological responses to ethanol and other drugs of abuse. Here, we provide an overview of physiological, pharmacological, and genetic research showing that: (A) administration of ethanol, as well as ethanol withdrawal, alter central NPY expression, (B) NPY modulates ethanol consumption under certain conditions, and (C) NPY signaling modulates the sedative effects of several drugs, including ethanol, sodium pentobarbital, and ketamine. Evidence suggesting possible mechanism(s) by which NPY signaling modulates ethanol consumption are considered. It is suggested that NPY may influence ethanol consumption by regulating basal levels of anxiety, by modulating the sedative effects of ethanol, and/or by modulating ethanol's rewarding properties.