Cigarette smoking, causing acute and chronic diseases, is a serious threat to the health of the public. The association of smoking with lung cancer was recognized first, but the relationship of smoking to cardiovascular disease was debated into the 1960s and early data from the Framingham cohort found no association. However, in 1962, an analysis combining the data from the Framingham men with the Albany, New York, male cohort found cigarette smoking predicted myocardial infarction, coronary heart disease mortality, and all-cause mortality. The same year, Framingham investigators wrote that smoking was a cardiovascular risk factor independent of other characteristics, such as blood pressure, cholesterol, and smoking cessation, and should be included in any prevention program. The first surgeon general’s report was released in 1964 and Framingham investigators were participants in the report’s development and provided important data on the association of cigarettes with cardiovascular disease. Subsequent analyses confirmed the early findings on the benefits of quitting for primary prevention of cardiovascular disease and secondary prevention after myocardial infarction. The Framingham investigators and cohort data played a crucial role in the current understanding of the dangers of cigarettes and the subsequent decline of smoking in industrialized countries.