Congenital heart defects (CHD) are a frequent cause of death and disability and cause a significant toll in terms of personal distress and social costs. The only satisfactory way of reducing this burden is through primary prevention, which in turn can be implemented only when the cause and mechanism of these defects is known. While current knowledge on the impact on the population and on the etiology and pathogenesis of CHD is still largely unsatisfactory, some progress has been made in recent times and promising research is currently being performed; these topics are discussed in this paper, with special emphasis on quantitative risk assessment of putative cardiac teratogens.