It is well established that atherosclerosis is caused by an inflammatory process in the arterial intima. However, it is only in recent years that it has become clear that this inflammation is modulated by immune responses against plaque antigens. These antigens are primarily believed to be modified self-antigens such as oxidized LDL. The immune system is challenged to determine whether these antigens should be regarded self and tolerated or non-self and eliminated. The latter will result in plaque development while the first will be protective. T cells are key effectors of both types of responses. An activation of regulatory T cells inhibits auto-reactive T effector cells and is anti-inflammatory. In contrast, if Th1 cells become activated in the plaque this is associated with increased inflammation and disease progression. The role of B cells in atherosclerosis remains to be clarified but some species of athero-protective antibodies have been identified. The elucidation of role of immune system in atherosclerosis has revealed new targets for intervention and both vaccines and antibody-based therapies are presently in or due to enter clinical testing.