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We evaluated literature that addresses the notion that flexible smoking treatment approaches are warranted for smokers with a diagnosis of schizophrenia. Understanding the biological and psychological mechanisms that increase the likelihood of smoking and decrease the motivation to quit for these individuals is addressed within the framework of a neurobiological model. We provide a brief overview of the limited smoking cessation treatment literature for patients with schizophrenia and compare abstinence-focused versus reduction-focused treatment modalities. The potential utility of the reduction-focused approach to tobacco treatment for these smokers is evaluated. Suggestions for future research to address the utility and efficacy of reduction-focused interventions for smokers with schizophrenia are put forth. We conclude with a consideration of the implications for the current understanding of smoking treatment among patients with co-morbid psychiatric diagnoses.