It has become increasingly clear that cancer can be considered neither purely genetic nor purely environmental. A relatively new area of cancer research has focused on the interaction between genes and environment in the same causal mechanism. Primary candidates for gene-environment interaction studies have been genes that encode enzymes involved in the metabolism of established cancer risk factors. There are common variant forms of these genes (polymorphisms), which may alter metabolism and increase or decrease exposure to carcinogens, thus impacting the risk of cancer. We present an overview of enzymes involved in carcinogen metabolism, present epidemiological tools to evaluate gene-environment interactions, and provide examples from cancers of the breast, lung and large bowel.