Neuropeptide Y (NPY) is an endogenous peptide neurotransmitter that exhibits a variety of properties, including vasoconstrictive/hypertensive, neuromodulatory, cognition enhancing, reward and reinforcement-modulating, antidepressant, anxiolytic, pro-angiogenic, and pro-atherosclerotic activities. NPY is produced by sympathetic nervous system neurons and activates Y receptors. In vivo, NPY potentiates reward- and reinforcement-inducing effects of opioids in operant behavior assays. In other animal models, NPY inhibits amyloid-β (Aβ)-induced depression and spatial memory deficits in the tail suspension and object location tasks. NPY also decreases or prevents stress-induced development of anxiety during the forced swim test and elevated plus maze models. Additionally, NPY promotes vascular growth and may play a role in the development of atherosclerosis.