Numerous studies have identified a role for the innate and adaptive immune response in atherosclerosis; both pro- and antiatherogenic roles for the immune responses have been demonstrated. Common autoantigens against which an immune response has been identified in experimental and human models of atherosclerosis include oxidized low-density lipopoteins, β2 glycoprotein 1 and heat shock protein 60. Activation of atheroprotective adaptive immune responses have been demonstrated for oxidized low-density lipoprotein-related antigens. Conversely, atheroprotection has been demonstrated with the induction of immune tolerance through activation of mucosal immunity to heat shock protein 65/60 and β2 glycoprotein 1. Recent identification of specific immunoreactive antigenic epitopes in the apolipoprotein B-100 component of low density lipoproetin and early experimental observations have provided proof of concept that active vaccination using specific apolipoprotein B-100-related antigens may emerge as a novel immunomodulating atheroprotective strategy.