There is widespread consensus that atherosclerosis is an inflammatory disease. Between possible pathogenetic mechanisms, infective hypothesis has received increasing attention. Researches have recently focused their attention on the role of Chlamydia pneumoniae, a gram-negative intracellular organism, as infection by this bacterium has been demonstrated frequently associated with atherosclerosis. This review attempts to analyze and critically evaluate available data of the literature about the association between Chlamydia pneumoniae and atherosclerosis in order to provide updated elements of judgement concerning a possible future revolutionary scenario: the consideration of atherosclerosis as an infective disease, susceptible to prevention and treatment by means of antimicrobial therapy. More than twenty sero-epidemiological studies have found a two-fold or greater risk of cardiovascular events in subjects with serological evidence of Chlamydia pneumoniae infection. The organism has been identified in over 50% of atherosclerotic plaques examined by various histopathological techniques, while it has been only rarely found in normal artery tissues; moreover, viable Chlamydia pneumoniae has recently been isolated from coronary and carotid atherosclerotic plaques. Several experimental studies have shown that the biological properties of Chlamydia pneumoniae can explain its potential role in initiating and/or modulating plaque formation. The most relevant issue, i.e. the possibility of preventing or slowing progression of the disease with antimicrobial treatment, is still unsolved: only data from experimental studies on animals and four small intervention trials on humans are available, and their encouraging results require confirmation in larger prospective studies. In conclusion, while the association between Chlamydia pneumoniae and atherosclerosis seems to be established, it is still uncertain whether or not the organism plays a causal role in atherosclerosis and its complications. It is hoped that the results of wide scale clinical intervention trials with antibiotics for the secondary prevention of atherosclerotic diseases now in progress will clarify this problem.