Neuropeptide Y (NPY) is a 36 amino acid peptide present in the brain, the adrenal medulla and peripheral sympathetic nerves. The localization and mode of release of NPY led to the proposal that this peptide plays an important role in modulating the contribution of the sympathetic nervous system to blood pressure control. In this paper Bernard Waeber and colleagues review the current knowledge about the mechanisms involved in NPY signal transduction and the different mechanisms whereby NPY, released by the peripheral nervous system, may influence vascular tone and cardiac function.