One of the challenges in environmental health is to attribute a certain health effect to a specific environmental exposure and to establish a cause-effect relationship. Molecular epidemiology offers a new approach to addressing these challenges. Mutations in the tumor suppressor gene p53 can shed light on past environmental exposure, and carcinogenic agents and doses can be distinguished on the basis of mutational spectra and frequency. Mutations in p53 have successfully been used to establish links between dietary aflatoxin exposure and liver cancer, exposure to ultraviolet light and skin cancer, smoking and cancers of the lung and bladder, and vinyl chloride exposure and liver cancer. In lung cancer, carcinogens from tobacco smoke have been shown to form adducts with DNA. The location of these adducts correlates with those positions in the p53 gene that are mutated in lung cancer, confirming a direct etiologic link between exposure and disease. Recent investigations have also explored the use of p53 as a susceptibility marker for cancer. Furthermore, studies in genetic toxicology have taken advantage of animals transgenic for p53 to screen for carcinogens in vivo. In this review, we summarize recent developments in p53 biomarker research and illustrate applications to environmental health.