New approaches to improve smoking cessation rates are needed. In recent years, substantial progress has been made in understanding the genetics of smoking behavior, and this knowledge may eventually be used to personalize treatment for smokers. Although there are highly significant and reproducible genetic associations, none are yet ready for clinical applications. We suggest that translational research from several disciplines, including behavioral science, ethics and economics, should be performed in parallel with ongoing genome-wide association studies for smoking behavior and pharmacogenetic trials. The coordinated effort of multidisciplinary research teams will help reveal the circumstances under which we can translate genetic insights into clinical practice in the hope of reducing the burden of smoking in society.