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Nicotine replacement therapies (NRTs) are efficacious smoking-cessation aids. However, only minimal increases in smoking cessation followed NRTs being made available over-the-counter (OTC), which presumably made these treatments more readily available. To better understand why the United States did not experience improvements in smoking cessation following the OTC availability of NRTs, it is useful to review factors that determine NRT's impact on smoking cessation and how these factors played out with the introduction of OTC NRT. The authors contend that for NRTs to have a greater impact on public health, increases are needed in the number of individuals making a quit attempt, the proportion using NRTs in a quit attempt, and the effectiveness of each quit attempt. Even small increases in the impact of OTC NRTs could yield significant benefits in terms of morbidity and mortality. The remainder of this article provides examples of interventions designed to target each of the aforementioned factors individually as well as examples of interventions that link increased cessation attempts, increased NRT reach, and increased NRT efficacy in order to synergistically enhance the impact of OTC NRTs.