Despite optimistic predictions when nicotine replacement therapy (NRT) was switched to over-the-counter (OTC) availability, population surveys have failed to demonstrate a positive impact on long-term smoking cessation. This review examined the strength of the evidence from randomised trials and comparison group studies supporting the effectiveness of OTCNRT. Twelve eligible studies were identified: OTCNRT was compared with placebo in four studies and with health professional-delivered NRT in four studies, and four studies involved community-based minimal intervention NRT. These studies were assessed systematically to determine their methodological quality and generalisibility to 'real-world' conditions of NRT use. The review found a number of issues, including provision of free NRT, heavy cigarette intakes (average 25 daily), high levels of personal interactions (7.6 per subject), lack of blindness assessment and failure of most studies to actively follow-up all subjects seriously limit the degree to which studies' results can be applied to non-research OTCNRT users. In addition, several important limitations affecting the meta-analyses of OTCNRT by Hughes et al. were highlighted. The review concluded that the superiority of OTCNRT over unaided smoking cessation has not been demonstrated convincingly. Future directions for research involve more innovative, rigorous controlled trials and prospective cohort studies where nicotine dependence is assessed adequately.