After defining “comorbidity,” the report briefly discusses documentation of the increased risk for drug-use disorder in youth with untreated attention deficit/hyperactivity disorder (ADHD). Evidence is then provided for classifying drug addiction as a mental illness under the criteria of the Diagnostic and Statistical Manual of Mental Disorders. The high prevalence of comorbid drug use and other mental disorders is indicated from multiple national population surveys since the 1980s. In discussing why drug-use disorders often co-occur with other mental illnesses, the report advises this does not mean that one caused the other regardless of the sequence. Three scenarios are offered for the linkage between drug-use disorders and other mental illnesses, with the report concluding that all three scenarios probably contribute to how and whether specific comorbidities occur. The next section of the report focuses on the link between tobacco use (nicotine addiction) and schizophrenia, with attention to research on how both nicotine and schizophrenia affect the brain. This is followed by a review of research on common factors in drug-use disorders and other illnesses. This research involves the search for genes that might predispose individuals to develop both addiction and other mental illnesses or to have a greater risk of a second disorder occurring after the first appears. Another focus of research on common factors pertains to the involvement of similar brain regions. Research on the influence of developmental stage is also discussed, including the long-term impact of early drug exposure. The report concludes with discussions of research pertinent to how comorbidity can be diagnosed and treated. Examples of promising behavioral therapies for patients with comorbid conditions are provided, and barriers to the comprehensive treatment of comorbidity are identified and discussed. A glossary and 19 references