Neuromodulation has been long thought to be important for regulating brain states, perception and decision making. Disregulation of neuromodulatory systems has been identified in several psychiatric diseases. Based on decades of work mainly in brain slices and anesthetized animals, we have accumulated a lot of knowledge of the molecular and cellular mechanisms of these neuromodulators. However, what is currently lacking is how these transmitters regulate perception and behavior. We now have the tools and methods to study these important questions.