For several decades, the study of substance use among adolescents has been extensively permeated by criminalization and stigma due to its associations with antisocial, delinquent, and risk-taking behaviors, which are common in this stage of life. Contrary to the traditional “Criminal Justice” approach, there is an urgent need to address this phenomenon as a progressive, chronic, relapsing, and treatable global mental health condition that requires a multidisciplinary and comprehensive approach to untangle its multifactorial nature. Throughout this chapter, an analysis will be performed using the “Public Health” framework, providing an evidence-based and biopsychosocial perspective that considers the critical developmental stage adolescents go through characterized by potential cognitive, emotional, behavioral and social disturbances that could impact adolescents’ quality of life. Furthermore, theoretical models and data will be presented to cautiously analyze the interrelation between substance use and delinquent behavior. This, in turn, will enable a better understanding of how to conduct a suitable needs assessment and designing of evidence-based programs. Lastly, prevention and intervention strategies, such as drug treatment courts, will be reviewed as possible responses by the Juvenile Justice System to guarantee the psychosocial well-being of adolescent offenders with substance use disorders.