This study investigates how family structure is associated with adolescent drug use and how parenting, peer use, religiosity, and neighborhood problems may mediate the relationship. The authors use structural equation modeling to examine the relationship between family structure and drug use across race, and examine potential mediators. Using data from a nationally representative sample of adolescents, the authors find that family structure has little impact on adolescent drug use once potential mediators are accounted for. Though there is minimal direct effect of family structure on adolescent drug use, family structure is significantly correlated with the four mediators. Although there is some variation in the impact of these mediators on adolescent drug use across race/ethnicity, comparison of structural models suggests these variations are not statistically significant. Possible limitations of the findings are discussed. (Contains 5 tables and 3 figures.)