The current study explored the relationships between parenting practices and adolescent drug use. Suburban middle school students (N = 2129) completed surveys that included measures of perceived parental monitoring, discipline and setting an anti-drug message as well as measures of drug-related knowledge, attitudes and peer norms. Results indicated that effective parenting practices had a direct protective effect in terms of adolescent drug use and that the protective effect of parenting practices remained significant after including the effects of parenting on adolescent drug-related knowledge, attitudes and perceived norms in a structural equation model. These findings suggest that effective parenting practices have a robust protective effect on youth drug use via multiple pathways that extend beyond parenting effects on the most proximal predictors of adolescent drug use.