There has been considerable attention in recent years to the intriguing hypothesis that coronary heart disease and other atherosclerotic diseases may be caused by infection with pathogens such as Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus. Supporting this hypothesis are studies that localize bacterial antigens to atherosclerotic plaques and that draw associations of systemic inflammation and chronic infections with coronary disease. Although there are several examples of positive associations of pathogen seropositivity with disease, recent prospective follow-up studies of infection seropositivity have not generally supported these associations. At present, the evidence is insufficient to designate infection as a causal risk factor for coronary heart disease. The results of ongoing larger observational studies and antibiotic treatment trials may yield important information regarding the presence and magnitude of risk, if any, beyond that conferred by established coronary risk factors.