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The co-occurrence of bipolar disorder and substance use disorders presents significant clinical challenges, complicating diagnosis, treatment, and prognosis. This review explores both psychosocial and psychopharmacological interventions evaluated in randomized, controlled trials to address this comorbidity. Findings indicate that while several interventions show promise, no single treatment is consistently effective across both mood and substance use domains as compared to placebo. These findings highlight the necessity of personalized, multimodal treatment plans tailored to the specific needs of individuals with comorbid bipolar disorder and substance use disorders. [Psychiatr Ann. 2024;54(9):e258–e262.] [ABSTRACT FROM AUTHOR]