People suffering from severe mental illnesses, such as schizophrenia and major affective disorders, have high rates of addictive behaviours related to alcohol and illicit substance use. This overview summarises new and old psychopathological issues on the comorbidity between mental and substance use disorder, the so-called ‘dual diagnosis’ phenomenon. It represents an unanswered challenge in terms of pathogenic models, treatment and long-term clinical management. Dual diagnosis is a complex and heterogeneous entity and a number of explanatory models of substance use among people with severe mental disorders have been proposed, aiming to test the ‘self medication’ hypothesis, the potential aetiological role of substance on occurrence of mental disorders, and the common underlying environmental, genetic and biological factors. Furthermore, in the literature attempts have been made to clarify psychopathological characteristics of people who suffer from dual diagnosis. Individuals with dual diagnosis appear to be more often males, with an earlier onset of the mental disorder and more severe clinical and social outcomes. The co-occurrence of mental and substance use disorders complicates treatment, management and prognosis of both disorders, but it remains often unrecognised and undertreated. Mental health and addiction professionals should accurately assess and evaluate this comorbidity, although aetiological links, temporal relationships and psychopathological characteristics are still not entirely clear and, probably, heterogeneous and multifactorial.