This chapter examines the relationship between bipolar and related disorders and substance use in adolescents, focusing on diagnostic criteria, prevalence, neurobiology, and neuropsychological aspects outlined in the DSM-5-TR. It explores how symptoms like mood instability and impulsivity increase the risk of substance use. Studies show that early-onset bipolar disorder during adolescence significantly elevates the likelihood of developing substance-related issues, creating a cycle of risk behaviors. Furthermore, adolescents with bipolar disorder display a heightened tendency to use substances for mood regulation. The chapter also addresses how excessive substance use exacerbates academic, occupational, and treatment adherence challenges in individuals with bipolar disorder. It concludes by stressing the importance of integrated psychosocial interventions to address both bipolar symptoms and substance use, aiming to improve treatment outcomes for adolescents.