Asbestos is a well-known toxin and lung carcinogen. Epidemiologic studies have established tobacco smoke and asbestos exposures synergistically interact to enhance lung cancer risk. The biologic mechanism responsible for this interaction has been the subject of considerable debate. Studies have suggested that asbestos may act as a carcinogen by generating free radical and reactive oxygen species, by inducing tissue injury and subsequent cellular growth, via large-scale chromosome loss and by enhancing delivery of tobacco carcinogens to the respiratory epithelium. Recent molecular epidemiologic approaches further suggest that asbestos enhances the mutagenicity of tobacco carcinogens and that it acts, at least in part, independent of the tissue damage responsible for fibrosis.