This Symposium, organized by the Center for the Assessment of Tobacco Regulations (CAsToR), aims to identify knowledge gaps in tobacco regulatory research that can be addressed by simulation (computational) modeling of tobacco behaviors, policies and health effects, identify the utility of and challenges in using models in the context of a dynamic tobacco landscape within the current tobacco regulatory framework, and propose a plan to fill knowledge gaps and address challenges in conducting timely TRS research that uses tobacco simulation modeling.