Fruits and vegetables contain phytochemicals (e.g., carotenoids, polyphenolics, anthocyanins, nitrogen- and sulfur-containing compounds) that target multiple neoplastic stages to reduce overall cancer risk. These phytochemicals induce cancer cell death through multiple mechanisms. Since tumors represent heterogeneous cell populations, such a multi-targeted approach offers an edge over the more prevalent therapeutic strategies that target single pathways. Our hypothesis is that whole food extracts rather than single phytochemicals offer optimal chemopreventive benefits, owing to the existence of natural synergistic networks among the constituent phytochemicals. These synergistic and cooperative interactions among bioactive constituents enable targeting of multiple pathways in a complementary and overlapping manner to facilitate superior chemopreventive action.