The accurate identification of risk factors is central to the development of effective efforts to prevent young people from using alcohol, tobacco and other substances. To date, a key limitation of the prevention literature has been the paucity of research that examines the extent to which substance use risk factors identified in studies of white adolescents generalize to African American (and other non-white) youth. In the absence of research on race differences in risk factor exposure and vulnerability, current preventive interventions are based on the implicit assumptions that 1) the risk factors for African American and white adolescents' substance use are identical; and 2) that African American and white adolescents are equally exposed and equally vulnerable to these risk factors. The purpose of the present study was to begin to examine empirically the equal exposure and vulnerability” assumption. Specifically, the paper used Hawkins, Catalano and Millers' widely cited 1992 article on risk and protective factors for adolescent and young adult substance use as a framework within which to review past risk factor research and as a guide to identify risk factors to examine for race differences in exposure and/or vulnerability. Based upon our review of the existing literature and our analysis of data from the University of Michigan's Monitoring the Future study, we conclude that the simple assumption that African American and white youth are equally exposed and vulnerable to the same risk factors is not correct. In fact, we found that African American and white seniors' differed significantly in their exposure to more than half of the 55 risk factors examined. Similarly, nearly one third of the 165 tests for race differences in vulnerability were highly significant (i.e., p < .01). While it is possible that some of the differences we identified resulted from chance, their consistency across variables, within the same risk factor domain, and across drug categories, makes the likelihood that our findings are primarily statistical artifacts unlikely. Based upon the results of this study it is clear that additional theoretically and empirically rigorous race-specific research is needed to better understand the etiology of substance use among African American adolescents. Further research is also needed to identify those risk factors that are most salient for African American adolescents and most amenable to change through well designed, and perhaps, culturally tailored preventive interventions.