Neuropeptide Y, one of the scions of the pancreatic polypeptide family, is found throughout the nervous system. Based on its abundance alone, one would expect neuropeptide Y to play an important role in the regulation of neuronal activity, and indeed many pharmacological studies have demonstrated neuromodulatory effects of neuropeptide Y. Here, William F. Colmers and David Bleakman review the known actions of neuropeptide Y on the electrical properties of nerve cells. Neuropeptide Y inhibits Ca2+ currents, and modulates transmitter release in a highly selective manner. Neuropeptide Y might be quite important in the regulation of neuronal state, as exemplified by its actions in the hippocampus and the dorsal raphé nucleus.