Atherosclerosis involves the formation of inflammatory arterial lesions and is one of the most common causes of death globally. It has been evident for more than 20 years that adaptive immunity regulates the magnitude of the atherogenic proinflammatory response. T cells may also influence the stability of the atherosclerotic lesion and thus the propensity for thrombus formation and the clinical outcome of disease. Immunization of hypercholesterolemic animals with low-density lipoprotein preparations reduces atherosclerosis, suggesting that vaccination may represent a useful strategy for disease prevention or modulation. This review summarizes our current understanding of the role immunity in atherosclerosis and outlines strategies for antigen-specific prevention of this disease.