Chronic and acute infectious diseases have been implicated in modifying the risk of atherosclerosis independently or in collaboration with conventional risk factors. During the past two decades, the discussion on microbial agents and atherosclerosis has mainly been centred on Chlamydia pneumoniae. The strongest evidence linking Chlamydia pneumoniae and atherosclerotic disease comes from in vitro experimental studies. In this review, we summarize and critically evaluate the available data of human diagnostic and therapeutic studies on the association of Chlamydia pneumoniae with atherosclerosis. Taking into account the human in vivo data, there is currently insufficient proof linking Chlamydia pneumoniae to atherosclerosis. At present, there are no indications for antibiotic treatment targeted at Chlamydia pneumoniae in the management of atherosclerosis.