Smoking cessation represents a very difficult task for the smoker, often requiring medical assistance. The introduction of smoking cessation drugs has been crucial to this process. Currently, there are two standardly used treatments: nicotine replacement therapy (NRT) and the antidepressant bupropion. Soon after their introduction, NRTs were sold over-the-counter (OTC), as oppose to on prescription, although in most countries, bupropion remains available only on prescription. Both prescribed and OTC NRTs have similar efficacy (i.e., their use approximately doubles the cessation rate among users and their use has shown a high level of economic rewarding). The most important advantage of OTC NRT is availability, as some patients may not be comfortable with the use of prescribed drugs. The introduction of OTC NRT has led to a substantial rise in their use, increasing the proportion of ex-smokers in the population. However, there are a lack of published, cost-benefit analysis data comparing prescription with OTC NRT. Considering the different economic, social and cultural conditions within particular countries, it is difficult to formulate a common optimal economic model for the distribution of NRT. Authentic studies and trials in this field in order to develop the appropriate policies in each particular country, are clearly required.