Lifetime history of major depressive disorder is more than double in ever smokers than in never smokers. Conversely, adjusted odds ratios of nicotine dependence are significantly elevated for major depressive disorder alone (3,11) or associated with an anxiety disorder (4,38). There is also a significant relationship between depressive symptoms' severity (CES-D) and ever smoking. A history of major depressive disorder is associated with a lower chance to quit smoking. One of the reasons is that smokers who try to quit smoking experience more withdrawal symptoms--including a depressive mood--and relapse more frequently if they have a history of major depressive disorder. Few trials experimenting the usefulness of antidepressants in smoking cessation were published. Only a limited trial concerning doxepin showed a significant action on withdrawal symptoms and abstinence rate at 4 weeks. Other trials with fluoxetine and moclobemide failed to show clearly a significant effect on abstinence rate, perhaps because the medication was initiated too soon before quit day. The nature of the association between smoking and depression has been explored in recent studies, which used a cohort follow-up or the evaluation of a female twin population. The conclusions were that there is probably no causal relationship but rather that the association arises largely from common familial factors that are probably genetic, at least in women. Concurrently, tobacco smoke has monoamine oxidase inhibitory properties, and smokers have lower monoamine oxidase activity than no smokers. Hence, it is possible that smoking has antidepressant properties. While smoking prevalence regularly decreases, one can assume that the relative risk of depressive disorder will increase in smokers.