The brain contains 2 major groups of dopamine neurons. One is located in the arcuate nucleus of the hypothalamic median eminence and is involved in neuroendocrine regulation. The other, which is the subject of this article, is located in the ventral mesencephalon and projects to the forebrain. Although dopamine neurons are few (<1/100 000 brain neurons), they play an important role in regulating several aspects of basic brain function. They are necessary for the normal tasks of the regions they innervate, including motor behavior, motivation, and working memory. Dopamine neurons are also a central element in the brain reward system that controls the learning of many behaviors. Disappearance of nigrostriatal neurons results in Parkinson disease, whereas blockade of dopamine receptors has therapeutic effects in psychosis. Finally, artificial increase in dopamine transmission is the common mechanism of action of drugs of abuse that leads to addiction. Understanding how dopamine works is a major goal of neurobiology. Much progress has been accomplished in identifying the intracellular signaling pathways that underlie the immediate actions of dopamine and account for its long-term effects on brain properties. Recent findings allow us to identify molecules that may represent future therapeutic targets in neurology and psychiatry.