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Medical and substance abuse comorbidity are highly prevalent and significant problems among people with serious mental illness. This article provides commentary on several articles in this special issue, and highlights some important issues involved in understanding the impact of dual disorders and in treatment needs. Data are presented that illustrate the ability of people with serious mental illness to provide reliable and valid information about their substance use and attitudes about their motivation and willingness to change. Questions are raised about the impact of motivation enhancement interventions, and the need for extrinsic motivation for change versus extrinsic motivation and environmental supports.