Bipolar disorder has a higher prevalence of substance use disorders comorbidity than any other psychiatric illness. Repeated epidemiological surveys have reported that people with bipolar disorder I and II have co-occurring substance use disorders with lifetime prevalence estimates ranging from 42% to 60%. Substance abuse may predispose to bipolar disorder and bipolar disorder may predispose to substance abuse, perhaps through self-treatment or through increased sensitivity to rewarding stimuli, or both disorders could arise from a common mechanism. Substance use in patients with bipolar disorder also contributes to excess morbidity and mortality. Bipolar patients with substance use disorders have a more severe course of mood disorder, including earlier onset, episodes that are more frequent, mixed episodes, hospitalizations and more complications, including anxiety- and stress-related disorders, aggressive behavior, legal problems, and suicide. Limited data for pharmacological interventions to manage concurrent drug and alcohol use in patients with bipolar disorder are available. Nevertheless, in most studies, medications for managing mood symptoms did not appear to have an impact on the substance use disorder. Pharmacotherapy for comorbid substance use disorder and bipolar disorder typically involves use of mood stabilizers or/and atypical antipsychotics, antidepressants and concomitant use of a medication specifically for the substance use disorder, e.g., naltrexone, acamprosate. Valproate seems to be a good treatment choice for patients with concomitant bipolar disorder and substance use disorders, as add on medication or alone. Carbamazepine, lamotrigine and topiramate are the other promising mood stabilizers in management of this comorbidity. Among antipsychotics mostly studied second generation antipsychotics are quetiapine and aripiprazole in bipolar patients with comorbid substance use. Antidepressants can be lifesaving in patients who are at risk for suicide whether they have a co-occurring substance use disorder. Literature encourages the clinicians that are working on this field about substance oriented medications use like buprenorphine, acamprosate, naltrexone as add on treatment. But level of evidence for literature make us think that we are still far away from the best treatment approach for co-occurring substance dependence and other psychiatric disorders. The field of bipolar disorder comorbid with substance use disorders is in need of large double-blind, placebo-controlled randomized studies. The lack of evidence in this field prevents experts to make clinical recommendations for most of this frequent comorbidity of bipolar disorder and substance use disorders. Treatment should maximize the use of psychosocial interventions and prescription of first-linemedications with proven efficacy in the context of recurrent alcohol and substance abuse.