The common co-occurrence of substance misuse and other psychiatric disorders and their intricate relationships have led to major community-based epidemiological studies in the US which showed high rates of current and lifetime comorbidity. Moreover, studies of clinical populations conducted in North America, Europe and Australia, showed even higher rates of comorbidity. The aetology of this comorbidity has also been investigated and important models have emerged with findings that inform its assessment and treatment. Future epidemiological studies should focus on the study of concurrent conditions rather than lifetime ones using research diagnostic instruments with high reliability providing information on a number of key outcomes.