Atherosclerosis is an inflammatory disease, and several antigens have been shown to activate the immune response and affect the development of atherogenesis. This suggests that modulation of the immune system could represent a useful approach to prevent and/or treat this disorder. A vaccination approach might be a useful, effective tool in the modern arsenal of cardiovascular therapy and could possibly be used on a large scale at a low cost. Several modalities of vaccines have been tested against lipoproteins, cholesterol, molecules involved in cholesterol metabolism, atherosclerosis-associated microorganisms, and other molecules (heat shock protein, CD99, vascular endothelial growth factor-receptor, interleukin-2), with promising results. Nevertheless, a deeper understanding of the role of immunization in atherosclerosis will be essential to the use of vaccines in clinical medicine.