Coronary heart disease (CHD) prevention has largely benefited in the past from the development of epidemiological research. However, the opposition association-causation is currently raised from observational data. We successively review, from some important examples, the classical methodological approach for discussing causality in epidemiology. The easy identification of DNA polymorphisms has prompted new CHD aetiological research in the past 10 years. Causality of the associations presents some special characteristics when genes are involved: necessity of replication, Mendelian randomization..., which might prove to be important in future research.