Serotonin is a modulatory neurotransmitter in the human brain that regulates mood, anger, reward, aggression, and appetite and plays a central role in brain development. These effects are mediated through the interaction of serotonin with at least 15 different receptor molecules. Through the development and careful characterization of novel radiotracers, we have been able to visualize and quantify in vivo many of the key molecular sites-including serotonin receptors, reuptake transporters, and enzymes-responsible for serotonin metabolism. The clinical goals of serotonin imaging are to aid in determining the pathophysiology of brain disorders, to determine novel therapeutic strategies, to predict treatment, to estimate risk, and to determine individualized dosing strategies. Despite the contradictory results of early studies, the field as a whole has made significant progress on nearly all of these fronts, and advances in methodology suggest paths toward coherence. Through concerted, directed, and cooperative efforts, the routine use of serotonin imaging in the clinic will most likely be achieved in the next decade.