Substance use disorders are exceptionally common in bipolar patients. Although the frequency of this co-occurrence is well-documented, the reasons for this association are not clear. In this review, the authors examine four potential hypotheses for why substance use and bipolar disorders co-occur: (a) substance abuse occurs as a symptom of bipolar disorder; (b) substance abuse is an attempt by bipolar patients to self-medicate symptoms; (c) substance abuse causes bipolar disorder; and (d) substance use and bipolar disorders share a common risk factor. None of these four hypotheses have unequivocal support for explaining all cases of bipolar and substance use disorder co-occurrence, and it is probable that all four mechanisms play some role in the excess of substance abuse observed in bipolar patients. Additional studies are warranted to clarify the complex relationships between these two conditions as better understanding of this co-occurrence could lead to better treatment for patients afflicted with both disorders.