Chemoprevention, a relatively new and promising strategy to prevent cancer, is defined as the use of natural dietary compounds and/or synthetic substances to block, inhibit, reverse, or retard the process of carcinogenesis. The chemopreventive effects elicited by these natural dietary compounds are believed to include antioxidative, anti-inflammatory activity, induction of phase II enzymes, apoptosis, and cell cycle arrest. Many mechanisms have been shown to account for the anticarcinogenic actions of natural dietary compounds; attention has recently been focused on intracellular-signaling cascades as common molecular targets for various chemopreventive natural dietary compounds. In this critical review, we will summarize current knowledge on natural dietary compounds that act through the signaling pathways and modulate gene expression to induce detoxifying enzymes, programmed cell death, anti-inflammatory, and anti-proliferative effects, thus providing evidence for these substances in cancer chemopreventive action (128 references).