Cereal foods constitute a backbone of human diet all over the world and are typically the most important sources of energy and dietary fiber intake. Cereals typically contribute about 50% of dietary fiber intake in western countries. A high whole grain (WG) intake has been consistently associated with reduced risk of developing type 2 diabetes, cardiovascular diseases, and colorectal cancer, mainly based on evidence from observational studies [1, 2]. A major challenge in this area of research is that the active components and the underlying mechanism have not been fully explored. Dietary fiber has been reported to be responsible for the health effects of WG consumption. Evidence from in vitro and rodent studies is emerging that, in addition to dietary fiber, the unique phytochemicals in WGs may in part contribute to these health-promoting effects. WGs are rich sources of various bioactive phytochemicals, which are structurally diverse secondary metabolites synthesized by plants. Different WGs may have different phytochemicals. The chemical profiles of the major WGs are still largely unknown. A major group of phenolic compounds in WG wheat and rye is the 5-n-alkylresorcinols (ARs). Among commonly consumed foods, ARs are present in high amounts only in the outer layer of wheat and rye. Avenanthramides (AVAs) and avenacosides A and B are phytochemicals unique to WG oats. To improve the understanding of WG foods for human health, there is a need to further study the roles of specific phytochemicals in WGs for chronic disease prevention.