BACKGROUND AND OBJECTIVE: Numerous studies have reported an association of coronary atherosclerosis and restenosis with certain bacterial and viral infections. This article reviews the pathophysiology of atherosclerosis, the role of infectious agents (i.e, cytomegalovirus and Chlamydia pneumoniae) in atherogenesis, and studies supporting the potential beneficial effects of antibiotics or antiviral agents in the management of atherosclerotic disease. DATA SOURCES: English-language clinical studies, abstracts, and review articles pertaining to infectious agents and coronary atherosclerosis. STUDY SELECTION AND DATA EXTRACTION: Relevant seroepidemiologic and pathologic studies and animal models evaluating the role of cytomegalovirus or C. pneumoniae in coronary atherosclerosis. DATA SYNTHESIS: Studies evaluating the possible role of cytomegalovirus and C. pneumoniae in the pathogenesis of atherosclerosis, as well as studies examining the use of antimicrobial and antiviral agents for reduction of cardiovascular events, are reviewed and critiqued. CONCLUSIONS: Current data do not allow us to determine whether infection is a cause or a cofactor of atherosclerosis. These uncertainties can he resolved by larger scale seroepidemiologic, pathologic, and interventional studies. Such efforts will contribute to identifying populations that are appropriate far particular surveillance or specific interventions, such as antibiotics or antiviral therapy.