Substance use among youth continues to be a public health concern. Effective prevention options require up-to-date and relevant theoretical frameworks and empirical studies that can help explain the etiology and correlates of substance use. The current proposal aims to develop the “Substance Use Normalization Theory” which is a promising and novel theoretical framework to explain adolescent substance use in contemporary society. At its basis, the normalization theory integrates elements from the Normalization thesis and Social Control Theory. Combined, these two frameworks create a unique synergy that predicts that in countries or historical time periods of high substance use rates, substance use is located outside the frame of deviance in the sense that it is not regarded as a violation of cultural codes or norms of adolescents. Thus, the Substance Use Normalization Theory predicts that during periods of high national prevalence rates, substance users are recruited from relatively conventional and non-deviant sections of the youth populations compared to when substance use prevalence rates are low. The proposed study will rigorously test the Substance Use Normalization Theory by using different data sets and novel methodologies. The theoretical framework and the empirical analyses aim to help researchers reach a better understanding of contemporary patterns of adolescent substance use, which in turn, promises to generate important information for policy makers across EU countries and member states.