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Three drugs are currently used as first line pharmacotherapy for smoking cessation, nicotine replacement therapy, bupropion and varenicline. Compared with placebo, the drug effect varies from 2.27 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 2.02, 2.55) for varenicline, 1.69 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.53, 1.85) for bupropion and 1.60 (95% <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content> 1.53, 1.68) for any form of nicotine replacement therapy. Despite some controversy regarding the safety of bupropion and varenicline, regulatory agencies consider these drugs as having a favourable benefit\/risk profile. However, given the high rate of psychiatric comorbidity in dependent smokers, practitioners should closely monitor patients for neuropsychiatric symptoms. Second\u2010line pharmacotherapies include nortriptyline and clonidine. 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