The objectives of this article are to review the prevalence, natural history, pathophysiology, and treatment of comorbid bipolar disorder with alcoholism and other psychoactive substance use disorders (PSUDs). 
 All identified bibliographies through a literature search of all Medline files and bibliographies of selected articles focusing on the prevalence, natural history, course, prognosis, inter‐relationship, and treatment of bipolar disorder with comorbid alcoholism and other PSUDs were reviewed. 
 Comorbidity of bipolar disorder and alcoholism and other PSUDs is highly prevalent. The presence of this so called ‘dual diagnoses’ creates a serious challenge in terms of establishing an accurate diagnosis and providing appropriate treatment interventions. The inter‐relationship between these disorders appears to be mutually detrimental. The course, manifestation, and treatment of each condition are significantly compounded by the presence of the other condition. Substance abuse and alcoholism appear to significantly complicate the course and prognosis of bipolar disorder resulting in increased suffering, disability, and costs. On the other hand, bipolar disorder may be a risk factor for developing PSUDs. Although, there are a number of hypotheses explaining the pathophysiological mechanism involved in such comorbidities, our understanding of the exact nature of such neurobiological mechanisms is still limited. While the antikindling agents and targeted psychotherapeutic techniques may be useful intervention strategies, there is still a significant lack of empirically based treatment options for these patients.