In this article, we summarize the multidomain evidence for the role of externalizing behaviors in the etiology of substance use disorders (SUDs). The focus is on two issues: (1) the mechanistic structure of the externalizing pathway as a complex multilevel developmental system encompassing behavior, neurocognitive and brain functional response systems, and social environment; and (2) the critical mediators and moderators of developmental course. The discussion of these issues is organized into three sections: (1) the core characteristics of the risk phenotype, (2) the epigenesis of risk and heterogeneity of developmental course, and (3) the probable neurocognitive and brain functional response systems and mechanisms underlying the risk phenotype. Although the majority of work covered pertains to risk for AUD, because of the evidence of a common underlying liability for all disorders of drug involvement (Kendler, Prescott, Myers, & Neale, 2003; Krueger et al., 2002), we have retained the generic SUD terminology when possible.
