Chlamydia pneumoniae, a respiratory pathogen, has been suggested as a risk factor for cardiovascular disease. Epidemiologic data are very controversial. Histopathologic and microbiologic studies have established an association between atherosclerosis and presence of C. pneumoniae, consistently finding C. pneumoniae DNA and antigens in atherosclerotic arteries. C. pneumoniae has been cultured from atherosclerotic arteries in several centers. An etiologic role for C. pneumoniae in initiation, acceleration of atherosclerosis, and/or acute ischemia remains debatable. In vitro studies have shown that C. pneumoniae can induce foam cell formation, low-density lipoprotein oxidation, and proinflammatory and procoagulant cytokine expression. Animal models of de novo initiation or enhancement of atherosclerosis have been developed. Preliminary trials of secondary prevention of coronary artery disease complications by antimicrobial agents show modest results. Better diagnostic tools, more diverse animal models, and clinical trials of primary prevention are needed. Meanwhile, results of ongoing large clinical trials on secondary prevention are eagerly awaited, but may not be definitive.