Understanding culture is an essential key to reducing tobacco use. Conceptualizations of culture vary across scientific disciplines and theoretical orientations. Because of the complexity of the causes and effects of tobacco use, no single discipline has sufficient capacity to undertake a comprehensive approach to studying culture and tobacco. Transdisciplinary research offers a means of bridging disciplinary perspectives. This paper reviews epidemiological data on observed variation in smoking patterns across national groups, ethnicities and genders, and presents reasons for studying culture in tobacco control research. We discuss and contrast conceptualizations and specific definitions of culture and identify aspects of each conceptualization that are relevant to research on tobacco. We present a multilevel, multidimensional conceptual framework for transdisciplinary research teams to use to think together about the influence of culture on tobacco and of tobacco on culture. The framework challenges researchers to think about how the sociocultural context influences tobacco use at micro, meso, and macro levels. Finally, we offer suggestions for improving transdisciplinary research on culture and tobacco.