Background and Aims: In 2017, the US Food and Drug Administration (FDA) proposed to reduce nicotine in cigarettes to minimally or non-addictive levels. This study qualitatively explored perceptions of nicotine and addiction, both independently and in response to messages communicating about nicotine reduction., Design: Qualitative study using focus groups. Participants described their perceptions of nicotine and addiction and their responses to messages about the nicotine reduction., Setting: Atlanta, GA and San Francisco, CA, USA. Semi-structured focus groups were conducted virtually in Spring 2020., Participants: Exclusive smokers (n = 27), dual users (of cigarettes and electronic cigarettes) (n = 25), former smokers (n = 32) and young adult non-smokers (n = 31)., Measurement: Inductive thematic analysis of transcripts was conducted, and results were compared across smoking status groups., Findings: Participants across all smoking status groups associated nicotine with tobacco products, but consistently misperceived that nicotine caused disease. Perceptions of addiction were largely negative and varied by smoking status. Experienced smokers (exclusive smokers, former smokers and dual users) differentiated tobacco use from other addictions and minimized their own experiences of addiction. Perceptions of addiction across experienced smokers included not only the chemical properties of nicotine, but also the behavioral aspects of tobacco use, including oral fixation, having a smoking routine and response to internal and external cues. In response to messages, many believed that removing the nicotine would not make cigarettes less addictive because of the multi-factorial nature of smoking addiction that includes non-pharmacological cues., Conclusions: Perceptions of nicotine and addiction among non-smokers, former smokers, exclusive smokers and dual users of cigarettes and e-cigarettes vary based on smoking status, but there is a common tendency to believe that nicotine is addictive, that addiction results from more than just nicotine, and that very low nicotine cigarettes will not necessarily reduce the addictiveness of cigarettes., (© 2021 Society for the Study of Addiction.)