Underuse of evidence-based treatment for smoking cessation, including use of nicotine replacement therapy (NRT), is widespread, particularly among minority smokers. This paper examines perceptions of NRT among and between racially and ethnically diverse groups of smokers. Nine focus groups were held among homogenous groups of African American, European American, and Hispanic smokers (N = 70). Specific themes included perceptions of: (a) the mechanism by which NRT works; (b) NRT development and regulation (ie, purpose and methods of clinical trials, Food and Drug Administration oversight, etc); (c) efficacy; (d) safety; and (e) overall cost effectiveness. Across all groups, there was a general lack of knowledge of NRT effects and its efficacy, with only moderate knowledge of the mechanism by which NRT works. Concerns about NRT safety were expressed in all groups, with particular apprehension about addictive potential and possible interactions with other medications. Among African American smokers in particular, there was strong suspicion of pharmaceutical industry and government oversight, which coincided with the consensus view that there are too many unknowns about NRT. Among Hispanic smokers, there was less suspicion of NRT but a strong cultural belief in personal responsibility for smoking cessation. Results highlight enduring misperceptions about NRT that likely undermine usage. More education about NRT is needed, not only about its efficacy and safety, but also with regard to its development and regulation. Health care professionals, many of whom are viewed as trustworthy sources of health information, have a particularly important role to promote wider use of proven cessation strategies.