Cancer chemoprevention involves the use of natural or synthetic compounds to reduce the risk of developing cancer. One of the potential strategies for preventing cancer in the human population is to use food-based natural products to induce cytoprotective enzymes, such as NAD(P)H:quinone oxidoreductase 1, glutathione S-transferase, superoxide dismutase, and heme oxygenase-1. The regulatory regions of these inducible genes contain the antioxidant response element (ARE), which is activated upon binding of the nuclear factor E2-related protein 2 (Nrf2) transcription factor protein. Nrf2 has been shown to be essential in the upregulation of these genes in response to oxidative stress and treatment with certain dietary phytochemicals. This review presents the current body of knowledge regarding the molecular mechanisms of Nrf2 regulation, and highlights the need for future investigations into how these mechanisms apply to natural product inducers of cytoprotective enzymes.