SummaryA historical review highlights an interest in the etiology of birth defects over the course of several centuries and recalls specific hypotheses on the origin of cardiovascular defects postulated 60 years ago. The “State of the Art” of the epidemiology of cardiovascular malformations is characterized by an expanding base of knowledge which holds promise for eventual preventive interventions. Epidemiologic investigations conducted in the past decade have led to an increased understanding of the benefits and problems of studies of populations and of methodologic issues in surveillance of disease and study of risk factors. Comparative evaluations of reported studies to an ongoing population-based case-control investigation (the Baltimore-Washington Infant Study) demonstrate variations in prevalence by time and place, evidence for a strong genetic predisposition to cardiac maldevelopment and new hypotheses regarding environmental risks in the home and place of occupation.