In this review the authors focus on the possible role of heat-shock proteins (hsp) in the immune pathogenesis of the atherosclerotic process. The authors discuss evidence showing increased expression of these proteins in the vascular wall of stressed and atherosclerotic vessels and the immune mechanisms which could justify some of the inflammatory aspects that are now currently recognized in atherosclerosis, namely some of the possible hsp immune activating properties and also the possibility of hsp representing an innocent auto-antigen which could be the unwanted target of an immune response, initially directed against microbial heat-shock proteins. Epidemiological evidence linking atherosclerosis and cardiovascular diseases to soluble hsp levels as well as the intensity of anti-hsp immune response is also reviewed.