Population-based studies have documented that among all patients with major psychiatric disorders, those with bipolar disorder have the highest prevalence of comorbid substance abuse and dependence. The cause of this high comorbidity rate has not been clearly established, and the relationship is probably bidirectional. Articles published in English from 1980 through 1997 containing the terms comorbidity, mania, outcome, and substance use were identified by searching Medline and then the bibliographies of the articles identified in this search. The literature review showed several risk factors to be associated with comorbid substance use disorders in bipolar disorder patients: early age of onset, gender, family history of substance use disorders, and presence of mixed mania. Methodological enhancements that have helped to advance understanding in this area include distinguishing between primary and secondary disorders, between the different subtypes of bipolar disorder, and between first and subsequent episodes of illness. In order to determine the temporal sequence of onset, longitudinal studies initiated at the onset of either illness need to be pursued. Increased understanding of the association between bipolar disorder and comorbid substance use disorder will facilitate improved detection and intervention, as well as more-effective preventive measures that could improve outcome for patients with bipolar disorder.