The prevalence of co-existing substance misuse and psychiatric disorder (dual diagnosis, comorbidity) has increased over the past decade, and the indications are that it will continue to rise. There have simultaneously been unprecedented developments in the pharmacological treatment of alcohol, opiate and nicotine misuse. Here we evaluate the evidence on the use of some of these treatments in dual diagnosis (with psychotic, mood and anxiety disorders). The evidence base is limited by the exclusion of mental illness when pharmacological agents for substance misuse are evaluated and vice versa. We set the available information within the context of the psychosocial management of comorbid substance misuse and mental illness, and the framework for service delivery recommended by UK national policy.