Our nosology defines substance use disorders by specific behaviors and their consequences. Yet current research, as exemplified in the article by Ersche et al. in this issue (1), is now based on the implicit assumption that addictive disorders depend on characteristics that preceded—and can be dissociated from—the behavior that defines them. Identifying these characteristics is part of a general strategy in psychiatric research to investigate underlying features (perhaps heritable) that predispose some individuals to more overt signs of a disorder. In fact, substance use may well be an epiphenomenon, albeit a potentially dangerous and toxic one, of a more pervasive neurobehavioral problem. For example, substance use disorders are highly prevalent in affective, anxiety, psychotic, and impulse control disorders (2). Therefore, susceptibility might be related to neural functions like the regulation of reward sensitivity, motivation, or arousal or to behavioral constructs like impulsivity or impaired decision making, which would underlie these conditions as well as substance use (3, 4). The Ersche et al. study used judiciously chosen markers for such characteristics, many of which were characterized in terms of underlying neural mechanisms (1).