The purpose of the present study was to examine how relationships among family, school, and peer factors relate to likelihood of substance use in Hispanic adolescents. Results indicated that only perceived peer substance use was directly related to adolescents' own substance use. A significant interaction was found between parental monitoring and peer use vis-à-vis substance use, which suggests that the relationship between parental monitoring and the adolescents' own use was significantly stronger among youth who reported that more of their friends used substances. Implications of these results for the design of substance use preventive interventions are discussed. Editors' Strategic Implications: This research is promising both in terms of the implications for targets of prevention programming and for the application of ecodevelopmental theory, which might guide similar efforts with different cultural groups.