Atherosclerosis is a histopathological process of a multifactorial origin. Whereas the genetic and biochemical causes received considerable attention, the involvement of the immune system has generally been considered negligible. In recent years evidence has been presented to support the dominant role played by the immune system in atherosclerosis. Two major antigenic determinants against which the immune response may be triggered have been suggested, namely the heat shock protein 60/65 and oxidized low density lipoprotein. The current paper reviews the data regarding the involvement of the immune system in atherogenesis with respect to the antigenic candidates mentioned above.