This paper presents a brief overview of our current understanding of the relationship between herpes simplex virus (HSV) and atherogenesis. In the search for a viral trigger of atherosclerosis, several investigators reported the detection of herpes simplex virus in some, but not all atherosclerotic lesions. HSV infections are very common, not only in atherosclerotic patients but also in the general population, making epidemiological studies difficult to interpret. Different mechanisms by which HSV may contribute to atherogenesis have been described. In vascular cells, HSV infection leads to lipid accumulation. HSV infection of endothelial cells attracts leukocytes with subsequent inflammatory damage; it activates procoagulant changes on endothelium with increased thrombin generation and platelet adhesion, and changes its interaction with extracellular matrix proteins. Future studies should delineate whether these mechanisms are operative in the pathogenesis of atherosclerosis.