Herein, we have described the background to the discovery that NRF2 is responsible for intrinsic resistance to many chemical carcinogens and that through its ability to mediate cellular adaption to oxidative and electrophilic stress it orchestrates induction of cytoprotective detoxification genes by cancer chemopreventive agents, thus inhibiting initiation of carcinogenesis in stomach, bladder, skin, GI tract, breast, lung and liver. This evidence concerns the gene NFE2L2 and cancer.