BACKGROUND Current smoking cessation treatments largely address pharmacological dependence on nicotine. New approaches are needed that address both nicotine dependence and psychological dependence on cigarettes as the source of nicotine. One such approach is the use of cigarettes with reduced nicotine content. METHODS We reviewed the available literature on the use of reduced-nicotine content cigarettes as a cessation aid. RESULTS One case series study and trial data indicate that reduction in the level of nicotine in cigarette tobacco can reduce the level of nicotine dependence in smokers and do so without adverse effects on cardiovascular biomarkers or significant compensatory smoking. We identified three clinical trials (total n = 489) that suggest that smokers can dissociate nicotine delivery from the act of smoking if they use reduced-nicotine content cigarettes in combination with nicotine replacement therapy. CONCLUSIONS The identified studies point to a benefit but involved only a small number of participants and provide only limited data on long-term abstinence. More definitive evidence from larger trials with longer follow-up is needed to clarify the role of reduced nicotine cigarettes as an aid to smoking cessation.