On a variety of fronts, chronic infection has been found to be significantly associated with the development of atherosclerosis and the clinical complications of unstable angina, myocardial infarction, and stroke. For the most part, these relationships are still just associations. Failure to confirm initial reports of serologic associations also has been common. Specific causative relationships on par with that determined between H pylori and peptic ulcer disease have not yet been established. Potential mechanisms whereby chronic infections may play a role in atherogenesis are myriad. In the case of C pneumoniae, the effect may result from direct vessel wall colonization that may damage the vessel either directly or indirectly by initiating immunologic responses. In other cases the effect may simply be that of enhancing the pre-existing chronic inflammatory response of the body to standard risk factors such as hyperlipidemia. Even though the infectious agent may not directly infect the vessel wall, it may perform its critical role from afar. Chronic infection might also influence pre-existing plaque by enhancing T-cell activation or other inflammatory responses that may participate in the destabilization of the intimal cap. Hence chronic infection may play a role either in the initiation, progression, or the destabilization of atherosclerotic plaques. The infectious agents with the most evidence to support an etiologic role in atherosclerosis include C pneumoniae and cytomegalovirus. Evidence is mounting for a variety of other potential agents including other herpes viruses, influenza, other specific bacteria (such as M pneumoniae), and chronic infections with common bacterial agents (periodontal disease, chronic bronchitis, and chronic urinary tract infection, among others) [191]. Future studies are expected to elucidate further the pathophysiologic relationship between chronic infection and atherosclerosis and to evaluate further the potential of a variety of treatment approaches, including antibiotics.