BACKGROUND: It may be reasonable to try to reduce the harm from continued smoking amongst smokers unable or unwilling to quit. Possible approaches to reduce the exposure to toxins from smoking include reducing the amount of tobacco used, and using less toxic products. The interventions evaluated in controlled trials have predominantly attempted to reduce the number of cigarettes smoked. OBJECTIVES: To assess the effect of interventions intended to reduce the harm from smoking on the following: biomarkers of damage caused by tobacco, biomarkers of tobacco exposure, number of cigarettes smoked, quitting, and long-term health status. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group Specialised Register using free text and MeSH terms for harm reduction, smoking reduction and cigarette reduction. The initial search was in March 2006, updated in March 2007. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of interventions in tobacco users to reduce amount smoked, or to reduce harm from smoking by means other than cessation. Outcomes were change in cigarette consumption, markers of cigarette exposure and any markers of damage or benefit to health, measured at least six months from the start of the intervention. DATA COLLECTION AND ANALYSIS: We pooled trials with similar interventions and outcomes using a fixed-effect model. Other studies were summarised narratively. MAIN RESULTS: The 13 included trials all evaluated interventions to help smokers cut down the amount smoked. Self-reported reduction in cigarettes per day (CPD) was validated by reduction in carbon monoxide (CO) levels. Most trials tested nicotine replacement therapy (NRT) to assist reduction. No eligible studies evaluated the use of potentially reduced-exposure products. In a pooled analysis of eight trials, NRT significantly increased the odds of reducing CPD by 50% or more for people using nicotine gum or inhaler or a choice of product compared to placebo (n=3273, odds ratio [OR] 2.02, 95% confidence interval [CI] 1.55 to 2.62). Where average changes from baseline were compared for different measures, CO and cotinine consistently showed smaller reductions than CPD. Whilst the effect for NRT was significant, small numbers of people in either treatment or control group successfully sustained a reduction of 50% or more. Use of NRT also significantly increased the odds of quitting (OR 1.90, 95% CI 1.46 to 2.47). One trial of bupropion failed to detect an effect on reduction or cessation. Four trials of different types of advice and instructions on reducing CPD did not provide clear evidence. AUTHORS' CONCLUSIONS: There is insufficient evidence about long-term benefit to give firm support the use of interventions intended to help smokers reduce but not quit tobacco use. Some people who do not wish to quit can be helped to cut down the number of cigarettes smoked and reduce their carbon monoxide levels by using nicotine gum or nicotine inhaler. Because the long-term health benefit of a reduction in smoking rate is unclear this application of NRT is more appropriately used as a precursor to quitting.