Adolescent substance abuse is a global problem which educators have sought to address through school-based preventive education. Prior research suggests that cultural sensitivity may mediate program success; however the ideal program composition remains unclear. Thus,the purpose of this review is to identify the cultural variables used in the adaptation of substance abuse prevention programs and to evaluate whether the inclusion of such variables enhance program outcomes. We reviewed 58 articles describing study design, results and the cultural variables involved. Cultural variables were categorized as surface-level variables (e.g. language, character names) and deep-level variables (e.g. normative beliefs, motivational factors). Empirical studies implied that variations in language, communication preferences, leve lof individualism, family orientation, religiosity, norms regarding substance use, gender, ethnic identity and environmental accessibility were possibly related to overall program success.Recommendations for future research and program modifications are discussed.