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Substantial progress has been made in recent years in the recognition and treatment of comorbid mental, substance abuse, and health disorders. In this article, we summarize this progress and consider next steps by addressing the following three questions, with a focus on persons with severe mental illness and substance use disorders: (a) What have we learned about comorbidity? (b) What are the advantages of focusing on comorbidity, and what are the costs? and (c) What are the future directions for research and treatment of comorbid disorders?