Both genetic and environmental factors influence coronary heart disease, therefore studies of coronary heart disease risk are often confounded by gene:gene and gene:environment interactions. Such interactions imply that at the molecular level there is synergy between the gene products or with the by-products of the environmental insult, resulting in a greater than additive effect on risk. Genetic risk is thus modifiable in an environment-specific manner. This review focuses on recently reported effects of smoking (environmental factor) on the impact of variation in the genes for glutathione S-transferase, paraoxonase and apolipoprotein E on the risk of coronary heart disease and effects on intermediate lipid traits. We end on a cautionary note for the need for repeat studies to confirm these reported gene:environment effects.