It is known that the interaction between substance use disorder (SUD) and bipolar disorder (BD) is complex. SUD is often seen as a risk factor for BD, but studies have also indicated that BD increases the risk of developing SUD. It is also known that the comorbidity between SUD and BD is highly prevalent in clinical and epidemiological settings, and individuals suffering from this comorbidity often present a worse clinical trajectory marked by functional and cognitive impairment. SUD is a preventable outcome and should be managed as early as possible in the clinical trajectory of individuals suffering from BD or at familial risk of developing BD. Thus, this chapter will discuss the evidence available on the impact of SUD in the course of BD, as well as discuss the clinical interventions available to manage this comorbid condition.