Emerging research will likely make it possible to tailor pharmacological treatment for individuals with tobacco dependence by genotype. This study explored primary care physicians' attitudes about the strengths of and barriers to using genetic testing to match patients to optimal nicotine replacement therapy. Four focus groups (n=27) were conducted, and data were analyzed using thematic content analysis. Physicians reported how likely they would be to offer patients a genetic test to tailor smoking treatment in response to three different scenarios that described characteristics of the genetic test based on published research. Respondents were on average 36 years of age; 59% were male and 67% were white. Physicians believed genetically tailored treatment may offer new hope to smokers trying to quit, yet they also noted several potential barriers to clinical integration. Barriers included erroneous assumptions by patients regarding the meaning of genetic test results, possible misinterpretation of information regarding racial differences in the prevalence of certain risk alleles, and potential discrimination against patients undergoing testing. Concerns increased dramatically when physicians were told that the same genotypes that would be identified to tailor smoking treatment also have been associated with increased risk of becoming addicted to nicotine, as well as other addictions and psychiatric disorders. Physicians were interested in the possibility of realizing improved smoking cessation outcomes through pharmacogenetic developments, but they also raised many concerns. Primary care physicians will need additional educational inputs and system support prior to integrating genetic testing for a common trait into their routine clinical practice.