Background There at least two reasons to believe antidepressants might help in smoking cessation. Depression may be a symptom of nicotine withdrawal, and smoking cessation sometimes precipitates depression. In some individuals, nicotine may have antidepressant effects that maintain smoking. Antidepressants may substitute for this effect. Objectives The aim of this review is to assess the effect of antidepressant medications in aiding long‐term smoking cessation. The drugs include bupropion; doxepin; fluoxetine; imipramine; moclobemide; nortriptyline; paroxetine; selegiline; sertraline, tryptophan and venlafaxine. Search methods We searched the Cochrane Tobacco Addiction Group trials register which includes trials indexed in MEDLINE, EMBASE, SciSearch and PsycINFO, and other reviews and meeting abstracts, in December 2002. Selection criteria We considered randomized trials comparing antidepressant drugs to placebo or an alternative therapeutic control for smoking cessation. For the meta‐analysis, we excluded trials with less than six months follow‐up. Data collection and analysis We extracted data in duplicate on the type of study population, the nature of the drug therapy, the outcome measures, method of randomization, and completeness of follow‐up. The main outcome measure was abstinence from smoking after at least six months follow‐up in patients smoking at baseline, expressed as an odds ratio (OR). We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. Where appropriate, we performed meta‐analysis using a fixed effects model. Main results There was one trial each of moclobemide, sertraline and venlafaxine, two of fluoxetine, five of nortriptyline, and twenty trials of bupropion. In the bupropion trials, 18 had a placebo arm, two of which tested long‐term use to prevent relapse. Nine of the bupropion trials have been published in full. Nortriptyline (five trials, OR 2.80, 95% CI 1.81 ‐ 4.32) and bupropion (16 trials, OR 1.97, 95% CI 1.67 ‐ 2.34) both increased the odds of cessation. In one trial the combination of bupropion and nicotine patch produced slightly higher quit rates than patch alone, but this was not replicated in a second study. Two trials of extended therapy with bupropion to prevent relapse after initial cessation have failed to detect a long‐term benefit. Authors' conclusions The antidepressants bupropion and nortriptyline can aid smoking cessation but selective serotonin reuptake inhibitors (e.g. fluoxetine) do not.