Epidemiologic evidence on the relation between genetic susceptibility and cancer is reviewed. Traditional epidemiologic studies have identified various exposure-related associations with cancer. Most conventional approaches to environmental and occupational cancer have not been able to address specifically the issue of individual susceptibility to the action of carcinogens. However, with the recent rapid advances in molecular biology, novel approaches to define the role of genetic susceptibility in epidemiologic studies of cancer etiology have emerged. Molecular epidemiology has begun to develop within the broad field of cancer research. Here, we provide a description of the current framework of this research. Ongoing studies of the associations of inheritable polymorphisms in metabolic genes with specific carcinogen exposures reflect the most active area of research. Future efforts will include the examination of inherited variation in DNA repair. Methods are being developed now that will allow for the application of linkage analysis to the problem of gene-environment interaction in cancer. These approaches hold considerable promise for defining the nature of genetic susceptibility to exposure-related cancers.