The Brisighella Heart Study (BHS) is a prospective, population-based longitudinal epidemiological investigation, which, at baseline enrolled 2939 randomly selected subjects (1491 men and 1448 women), aged 14–84 years, free of cardiovascular disease at enrollment, resident in the northern Italian rural town of Brisighella. The study was initiated in 1972 and it is still active, planning its 11th four-yearly population survey in 2012. The observational phase of the study contributed to the evidence of a strong physiopathological link between hypercholesterolemia and hypertension, while the interventional phase was one of the first examples of successful cardiovascular risk reduction obtained through an educational intervention on a whole population. Today, the classical epidemiological study is evolving in the direction of advanced biomolecular analyses, genetic tests and functional vascular investigations. This article reviews published data from the BHS and will describe the evolution of a classical epide...