The chapter addresses obsessive-compulsive disorder and its relationship with substance use during adolescence, exploring clinical, neurobiological, and psychosocial aspects. In the DSM-5-TR, the disorder is defined by the presence of obsessions, consisting of intrusive thoughts or images, and compulsions.In adolescence, this condition is complex and can lead to significant impairments in psychosocial well-being and functioning. Genetic and environmental causes are examined, as well as alterations in brain circuits and neuropsychological difficulties in executive functions, memory, and processing speed. The chapter also discusses the high prevalence of comorbidities, such as anxiety and depression, and the association between obsessive-compulsive disorder and substance use, with a focus on alcohol and cannabis. This relationship often reflects the use of substances as a coping strategy to alleviate emotional distress. The conclusion highlights the importance of comprehensive psychosocial interventions that address the specificities of this relationship in adolescence.