Polyphenols are the most abundant antioxidants in our diet. The pro-oxidant/antioxidant balance is believed to be an important determinant of the immune cell function as the rather high percentage of polyunsaturated fatty acids (PUFAs) in their cell membranes has made the immune cells particularly sensitive to oxidative stress. Polyphenols as dietary antioxidants may affect various aspects of both innate and adaptive wings of the immune system by shifting pro-oxidant/antioxidant balance toward antioxidant. Complement system, for instance, has been shown to be inhibited by polyphenols and this complement inhibitory effect may have some role in anti-inflammatory properties of polyphenols. The anti-inflammatory effects of polyphenols, which may be exerted at the molecular level, are likely to be dependent on the specific structure of polyphenolic compounds. Macrophage functions, including cytokine production, may also be affected by some flavonoids through modulation of inducible cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS). Many experimental studies have reported immune modulating effects of polyphenolic compounds on both humoral and cell-mediated adaptive immunity. On the other hand, oxidative stress has been proposed as to play a role in many clinical conditions including allergy, cancer, and atherosclerosis, among others. Many experimental as well as human studies have supported the prophylactic effects of polyphenols against these pathologies. These data altogether suggest that the effects are exerted through antioxidant-mediated immune modulation mechanisms. On the other hand, polyphenolic compounds may act as a pro-oxidant under certain situations and this may in part explain the inconsistencies often seen in results of different studies. Finally, the results of most, notably in vitro, studies on polyphenols and immunity can be hardly interpreted as to long-term general health of human. Therefore, further laboratory and clinical studies are still needed to clarify the effects of polyphenolic compounds on the immune function as well as on health status.