In the present historical review, we highlight several papers outlining contributions of the Framingham Heart Study (FHS) over the span of nearly 7 decades to our understanding of the epidemiology of blood pressure (BP), atrial fibrillation, and genetic factors as they relate to cerebrovascular disease. In 1970, Framingham investigators led by William Kannel explored the epidemiological relations of BP and its various components to risk of ischemic stroke as well as hemorrhage, and they noted the greater impact of hypertension to risk of stroke compared with other cardiovascular outcomes. Framingham investigators changed the prevalent concepts in terms of the contribution of BP components to stroke risk; that is, they showed systolic pressure to be no less important a component for stroke risk than the diastolic or mean arterial pressures. In addition, they challenged the notion that hypertension was a normal consequence of increasing age, as connoted by the term essential hypertension. They also refuted the idea that BP elevation in the elderly population is innocuous by demonstrating that increased stroke risk persisted in advanced age in hypertensive persons. Thirty years later, the Framingham study attained long-term follow-up of an entire generation of participants with excellent retention to follow-up, thus providing an opportunity to study hypertension and risk of stroke in a general population sample. Framingham investigators examined the effect of various BP components over a 50-year follow-up in normotensive and untreated hypertensive individuals as regards stroke risk and showed the long-term importance of antecedent (midlife) hypertension in future stroke risk. Similarly, by calling attention to the importance of chronic nonvalvular atrial fibrillation as a contributor to stroke, particularly in the elderly population, FHS investigators confirmed the clinical observations of the founder of stroke neurology, C. Miller Fisher, MD, who had made the clinical and pathological association of atrial fibrillation to stroke. Lastly, in the dawn of the era of individualized preventive medicine, FHS is participating in the effort to further our understanding of the role of genetic factors to stroke incidence. The contributions of FHS have been many and have shaped our understanding of the relation of BP, atrial fibrillation, and other risk factors to stroke risk, thereby setting the stage for clinical trials that demonstrated how control of these risk contributors could prevent stroke and enable stroke prevention. FHS investigators are collaborating with other geneticists and epidemiologists internationally to elucidate the role of genetic factors and stroke susceptibility, which is likely to continue to shape the practice of preventive cardiovascular medicine.