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The challenge of reducing smoking in people with serious mental illness. The high prevalence of smoking in people with serious mental illness contributes substantially to the disproportionately high morbidity and premature mortality in this population. There is an urgent need to help people with serious mental illness to quit smoking. We discuss competing explanations for the high prevalence of smoking in people with serious mental illness and the effectiveness of available smoking cessation interventions. We propose trials of harm reduction options, such as nicotine replacement therapy and electronic cigarettes (e-cigarettes), as long-term substitutes for cigarettes in smokers with serious mental illness who are unable to quit smoking. We also propose that smoke-free psychiatric units provide smoking cessation support on patient admission to the hospital and after discharge.