Despite decades of research aimed at improving the effectiveness of smoking treatment, available treatments are only modestly effective, and smoking remains the leading cause of preventable deaths in the United States. Recent research on genetic factors related to smoking behavior eventually may lead to the design of new tobacco dependence treatments and to the individualization of treatment based on genetic factors. Although this research is in its infancy, and data on the analytic and clinical validity of genetic tests to tailor smoking treatment are not yet available, it is not too soon to begin identifying and addressing key ethical issues associated with genetic testing in the context of tobacco dependence treatment. Key concerns include (a) potential harm (e.g., stigmatization, discrimination) to patients related to inappropriate use of genetic information, (b) implications of pleiotropic associations, (c) differential prevalence of risk-conferring genotypes among racial or ethnic subpopulations, (d) preparedness of primary care physicians to incorporate genetic testing into smoking treatment, (e) informed consent, and (f) ensuring an appropriate balance between individually tailored treatment by genotype and broad-based interventions that focus on social and environmental factors affecting smoking behavior. Additional research on these ethical and social issues must be conducted simultaneously with the scientific work currently under way. Failure to address these concerns will likely undermine efforts to translate knowledge emerging from the United States' substantial investment in genetic research on smoking into clinical practice and improved patient outcomes.