Objective: The current introductory article provides the rationale for the special section on understudied smokers and innovative treatments. This article proposes a definition of "special populations" of smokers, outlines a priori criteria by which to judge whether an intervention should be adapted for these smokers, and delineates a process by which cultural adaptation of an intervention can be achieved. Next steps for innovative, theory-based treatments with special populations and with general populations of smokers are discussed. Method: Special populations of smokers are defined as having (a) greater than 10% higher smoking prevalence than the general population of smokers, (b) disproportionate tobacco-related health disparities, (c) less access to treatments, and (d) a lack of prospective, longitudinal treatment trials. Results: Cultural adaptation of evidenced-based treatments (EBTs) for underserved smokers should be applied more widely, outside the bounds of race and ethnicity, but also judiciously, following several a priori criteria. Cultural adaptation may be justified if the target population differs from the general population in (a) rates and patterns of smoking, (b) burden of tobacco-related health diseases, (c) predictors of smoking behavior, (d) risk factors for treatment failure, (e) protective factors that facilitate quitting, (f) treatment engagement, (g) treatment response, and (h) perceived social validity of the EBT. Once these criteria are met, four phases of cultural adaptation of an EBT for the target population are proposed. Innovative treatments need to be developed that use novel channels and linkages between channels; test novel theories or build on mechanisms research to more accurately pinpoint targets of change; and increase consumer demand for EBTs. Conclusion: The process of cultural adaptation should be thoughtfully conducted with a priori definitions and criteria as well as standardized processes. Coupled with innovative, theory-based treatments, these considerations could help to jump-start stalled smoking cessation rates. (Contains 3 tables and 1 figure.)