The aims of this review were to examine the rationale for investigating the interaction between genes and the environment and to discuss recent studies into the interactions of genes and environmental modulators that are relevant to cardiovascular disease and its principle risk factors. Studies that have focused on smoking, alcohol and coffee consumption, and physical activity have all been observational studies and have involved relatively large samples. However, they tended to examine single genes and failed to take into account interactions with other genes or associated environmental factors. Both observational and interventional studies have been used to explore the interaction between genes and diet, with interventional studies being much smaller. Of the gene-diet interactions reported, two important highlights are, firstly, the confirmation that the apolipoprotein A-V gene (APOA5) is involved in triglyceride metabolism and is modulated by dietary factors and, secondly, the discovery that apolipoprotein A-II (APOA2) modulates food intake and the risk of obesity. The study of gene-environment interactions is an active and vital area of research. While the technical barriers to carrying out genetic studies are rapidly being overcome, studies are still hampered by the substantial difficulty of including comprehensive and reliable data on environmental factors. Progress in this area depends on involving large study populations across a range of geographical regions, as well as on employing a more comprehensive, standardized and precise approach to acquiring information about environmental factors.