This chapter explores the complex relationship between substance use disorder (SUD) and bipolar disorder (BD), highlighting common features between these conditions and their clinical impact. Initially, shared genetic markers and risk factors associated with the co-occurrence of these disorders are examined. Subsequently, the adverse effects of SUD on the course and prognosis of BD are discussed, including increased severity of mood episodes, more frequent hospitalizations, and higher suicide risk. Additionally, predictive models suggesting a possible association between SUD and subsequent BD development over time are presented. Recent genomic research is scrutinized to elucidate the shared genetic architecture between BD and SUD, highlighting challenges and opportunities in understanding these disorders. Strategies to mitigate substance use in individuals at risk of BD are also discussed, including behavioral and therapeutic approaches, as well as public health interventions and protective factors. This chapter aims to provide a comprehensive overview of the interplay between SUD and BD, identifying key areas for future research and clinical practice.