Numerous herbal and dietary agents have been recognized as cancer chemopreventive agents because of their anticarcinogenic activity. These compounds function as anti-oxidants and exert their antitumor activities through regulation of different cell signaling transduction pathways, which are involved in cancer growth, invasion and metastasis. By regulating the cell signaling transduction, these dietary compounds can sensitize cancer cells to apoptotic cell death. Therefore, conventional cancer therapies combined with these dietary compounds may exert enhanced antitumor activity through synergistic mechanism of action. The use of some of these chemopreventive agents has been investigated to potentiate the therapeutic effect of radiotherapy for cancer. This novel therapeutic approach will be discussed in light of recent and original findings on radiosensitization of prostate cancer by soy isoflavones in vitro and in preclinical animal tumor models, in vivo. We will address the molecular mechanism of interaction between soy isoflavones and radiation and discuss signal transduction survival pathways activated by radiation, which are inhibited by soy isoflavones, thus resulting in increased cell death.