Twins have fascinated human communities since the beginning of recorded history. In cardiovascular research, twin studies played a pivotal role in the discovery of the genetic basis of coronary artery disease, myocardial infarction and most of their associated risk factors. Matched for age, prenatal and postnatal environmental factors, discordant monozygous twin pairs provide a means to enhance the power to analyse epigenetic and metagenomic mechanisms. In the near future, combining the monozygous discordant twin study design with the recent advance of the sequencing technologies it will be possible to explore the complexity of the gene-environment relationships and individual variability to provide important insights into the pathogenesis of coronary artery disease/myocardial infarction.