The Department of Epidemiology in the Johns Hopkins School of Hygiene and Public Health was founded in 1919, with Wade Hampton Frost as its inaugural Chair. In our Centennial Year, we review how our research and educational programs have changed. The early years focused on doctoral education in epidemiology and some limited undergraduate training for practice. Foundational work on concepts and methods linked to the infectious diseases of the day made major contributions to study designs and analytical methodologies, largely still in use. With the epidemiologic transition from infectious to chronic disease, new methods were developed. The Department of Chronic Diseases merged with the Department of Epidemiology in 1970, under the leadership of Abraham Lilienfeld. Leon Gordis became Chair in 1975 and multiple educational tracks were developed. Genetic epidemiology began in 1979 followed by advances in infectious disease epidemiology following the HIV/AIDS epidemic. Collaborations with the Department of Medicine led to the development of the Welch Center for Prevention, Epidemiology and Clinical Research in 1989. Between 1994 and 2008 the Department experienced rapid growth in faculty and students. A new methods curriculum was instituted for upper-level epidemiologic training in 2006. Today's research projects are increasingly collaborative, taking advantage of new technologies and methods of data collection, responding to "big data" analysis challenges. The Department continues to address issues of disease etiology and epidemiologic practice in our second century.