In this article, I provide a perspective on the tobacco epidemic and epidemiology, describing the impact of the tobacco-caused disease epidemic on the field of epidemiology. Although there is an enormous body of epidemiologic evidence on the associations of smoking with health, little systematic attention has been given to how decades of research have affected epidemiology and its practice. I address the many advances that resulted from epidemiologic research on smoking and health, such as demonstration of the utility of observational designs and important parameters (the odds ratio and the population attributable risk), guidelines for causal inference, and systematic review approaches. I also cover unintended and adverse consequences for the field, including the strategy of doubt creation and the recruitment of epidemiologists by the tobacco industry to serve its mission. The paradigm of evidence-based action for addressing noncommunicable diseases began with the need to address the epidemic of tobacco-caused disease, an imperative for action documented by epidemiologic research.