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Among the mentally ill, smoking prevalence is highest in patients with schizophrenia (∼70–80%). This can impose a significant financial burden on patients, not to speak of increased smoking-related morbidity and mortality. Therefore, it is critical for clinicians to understand why patients with schizophrenia smoke in order to adapt treatment schemes. Understanding the reasons may also help to develop new drugs that target the nicotinic system in the brain as well as smoking cessation programs that are specifically designed for this particular patient population.So far, several reasons have been identified which are believed to explain tobacco consumption in patients with schizophrenia. Originally, it was widely believed that patients with schizophrenia smoke to increase hepatic clearance and to restore the dopamine blockade of certain antipsychotic drugs to diminish their side effects. However, more recently it became obvious that cigarette smoking may also be reinforcing for patients because it improves psychiatric symptoms, most notably negative and cognitive symptoms. The underlying molecular mechanisms of these nicotine effects are currently under intensive investigation.Heavy smoking in schizophrenia cannot simply be viewed as a ‘bad habit’. Rather, self-medication of clinical symptoms and side effects of antipsychotic drugs appear to play a major role.