Although extensive resources are dedicated to the development and study of cancer drugs, the cancer burden is expected to rise by about 70% over the next 2 decade. This highlights a critical need to develop effective, evidence-based strategies for countering the global rise in cancer incidence. Except in high-risk populations, cancer drugs are not generally suitable for use in cancer prevention owing to potential side effects and substantial monetary costs (Sporn, 2011). There is overwhelming epidemiological and experimental evidence that the dietary bioactive compounds found in whole plant-based foods have significant anticancer and chemopreventative properties. These bioactive compounds often exert pleiotropic effects and act synergistically to simultaneously target multiple pathways of cancer. Common bioactive compounds in fruits and vegetables include carotenoids, glucosinolates, and polyphenols. These compounds have been shown to target multiple hallmarks of cancer in vitro and in vivo and potentially to address the diversity and heterogeneity of certain cancers. Although many studies have been conducted over the past 30 y, the scientific community has still not reached a consensus on exactly how the benefit of bioactive compounds in fruits and vegetables can be best harnessed to help reduce the risk for cancer. Different stages of the food processing system, from "farm-to-fork," can affect the retention of bioactive compounds and thus the chemopreventative properties of whole foods, and there are opportunities to improve handling of foods throughout the stages in order to best retain their chemopreventative properties. Potential target stages include, but are not limited to, pre- and postharvest management, storage, processing, and consumer practices. Therefore, there is a need for a comprehensive food-system-based approach that not only taking into account the effects of the food system on anticancer activity of whole foods, but also exploring solutions for consumers, policymakers, processors, and producers. Improved knowledge about this area of the food system can help us adjust farm-to-fork operations in order to consistently and predictably deliver desired bioactive compounds, thus better utilizing them as invaluable chemopreventative tools in the fight to reduce the growing burden of cancer worldwide.