The epidemiological approach to investigation of cardiovascular disease was innovated in 1948 by Ancel Keys' Seven Countries Study and T.R. Dawber's Framingham Heart Study. Conducted in representative samples of the general population, these investigations provided an undistorted perception of the clinical spectrum of cardiovascular disease, its incidence and prognosis, the lifestyles and personal attributes that predispose to cardiovascular disease, and clues to pathogenesis. The many insights gained corrected numerous widely held misconceptions derived from clinical studies. It was learned, for example, that the adverse consequences of hypertension do not derive chiefly from the diastolic pressure, left ventricular hypertrophy was not an incidental compensatory phenomenon, and small amounts of proteinuria were more than orthostatic trivia. Exercise was considered dangerous for cardiovascular disease candidates; smoking, cholesterol, and a fatty diet were regarded as questionable promoters of atherosclerosis. The entities of sudden death and unrecognized myocardial infarction were not widely appreciated as prominent features of coronary disease, and the disabling and lethal nature of cardiac failure and atrial fibrillation was underestimated. It took epidemiological research to coin the term "risk factor" and dispel the notion that cardiovascular disease must have a single origin. Epidemiological investigation provided health professionals with multifactorial risk profiles to more efficiently target candidates for cardiovascular disease for preventive measures. Clinicians now look to epidemiological research to provide definitive information about possible predisposing factors for cardiovascular disease and preventive measures that are justified. As a result, clinicians are less inclined to regard usual or average values as acceptable and are more inclined to regard optimal values as "normal." Cardiovascular events are coming to be regarded as a medical failure rather than the first indication of treatment.