Phenolics including many polyphenols and flavonoids have the potentials to become chemoprevention and chemotherapy agents. However, poor bioavailability limits their biological effects in vivo. This paper reviews the factors that affect phenolics absorption and their bioavailabilities from the points of view of their physicochemical properties and disposition in the gastrointestinal tract. The up-to-date research data suggested that solubility and metabolism are the primary reasons that limit phenolic aglycones bioavailability although stability and poor permeation may also contribute to the poor bioavailabilities of the glycosides. Future investigations should further optimize phenolics bioavailabilities and realize their chemopreventive and chemotherapeutic effects in vivo.