A short review of research on the relationship between crime, substance abuse and mental disorders is given. A majority of studies unequivocally support the conclusion that abusers of psychotropic substances commit a vast amount of crime, partly related to the need for purchasing drugs but also involving other criminal behaviours including serious violent crimes and homicide. It is still frequently overlooked that multiple disorders together with a complex variety of other conditions and circumstances are characteristic among criminal offenders. The modern forensic psychiatric assessment of responsibility requires a multiaxial polydiagnostic approach including all aspects of comorbidity. From 1989 to 1994, in the Basel Forensic Psychiatric University Service, 450 offenders were assessed for responsibility, and 83% showed a substance-related disorder. 38% of them had two diagnoses, 29% three diagnoses and 10% more than three diagnoses. The most frequent comorbidities were combinations of substance-related disorders with personality disorders and schizophrenia. We found a clear connection of comorbidity and likelihood of diminished responsibility or irresponsibility. The scope and requirements for future research on comorbidity in forensic psychiatry are discussed.