Objective: Comorbid ADHD and substance use disorder (SUD) presents frequently in adolescence, a developmental period that may promote the emergence of substance misuse among individuals with ADHD. Comorbid ADHD and SUD in adolescence results in significant and unique treatment challenges, necessitating examination into effective interventions. Method: This systematic review examined existing research into the treatment of comorbid adolescent ADHD and SUD. Results: Findings from a small number of pharmacological intervention studies suggest potential efficacy of extended-release stimulant and nonstimulant medications. Efficacy of psychotherapeutic interventions has not been systematically examined. Conclusion: Current research on treatments for comorbid ADHD and SUD in adolescence is limited. Future placebo-controlled clinical trials using large samples are needed to examine the efficacy of psychotherapeutic interventions, the heightened risk of prescription stimulant misuse, and the long-term maintenance of treatment gains in this population. Clinical guidelines for the treatment of comorbid ADHD and SUD are discussed.