This chapter addresses schizophrenia spectrum and other psychotic disorders in adolescents, according to the diagnostic criteria of the DSM-5-TR, with a focus on their relationship with substance use. The prevalence of these disorders among adolescents, although rare, increases with age, significantly affecting psychosocial functioning and impairing academic and occupational performance. The etiology is multifactorial, involving genetic, neurobiological, and environmental factors. Dopaminergic alterations in key circuits such as the thalamus, cerebral cortex, and striatum, along with imbalances in glutamate and GABA, are linked to cognitive and negative symptoms. Neuroanatomical changes, such as reduced cortical volume and alterations in white matter, are associated with cognitive impairments, including memory and executive function impairments. Comorbidities, such as substance use, exacerbate the clinical course of these disorders, increasing the risk of worsening psychotic symptoms, poor treatment adherence, and suicidal behaviors. The chapter concludes by emphasizing the importance of comprehensive psychosocial interventions that address both psychotic disorder symptoms and substance use, underscoring the need for integrated approaches to improve treatment outcomes in adolescents.