Established cardiovascular risk factors do not fully explain the variations in the prevalence and severity of coronary heart disease. Recent evidence suggests that common chronic infections may contribute, either by direct or indirect mechanisms, to the etiology and/or progression of coronary atherosclerosis. Of the candidate infectious agents implicated, Chlamydia pneumoniae has emerged as the most likely pathogen to have a causal role. Evidence for this is based on seroepidemiologic, pathologic, and laboratory-based evidence, in addition to recent small-scale antibiotic intervention studies. Concerted efforts are now focused on the design of large prospective trials with antibiotics active against C. pneumoniae in the secondary prevention of coronary heart disease.