The role of inflammatory mechanisms in the initiation, progression and clinical expression of atherosclerosis is increasingly appreciated. With this awareness, the possibility that acute or chronic infection may initiate or modulate these processes is an active area of investigation. Infectious organisms may influence the atherosclerotic process through direct local effects on the coronary endothelium, on vascular smooth muscle cells and on macrophages in the atherosclerotic lesion. Infection may also exert systemic effects by inducing the elaboration of cytokines, the creation of a hypercoagulable state and by activating monocytes, causing possible transmission of infectious material to atherosclerotic lesions. Macrophages may then elaborate multiple mediators which destabilise plaque, promoting rupture and progression. Seroepidemiological data have identified associations between clinically active atherosclerosis and evidence of infection with Helicobacter pylori, Chlamydia pneumoniae and some herpesviridae. In addition, pathological examinations have demonstrated the presence of infectious organisms in coronary artery plaques. Cytomegalovirus, for example, has been identified pathologically to be associated with transplant vasculopathy and with an increased risk of restenosis following coronary intervention. Finally, recent pilot trials have demonstrated that macrolide antibacterial treatment directed against C. pneumoniae reduces the risk of recurrent coronary events. Infectious organisms may therefore influence atherogenesis through multiple pathways, and pathological and seroepidemiological investigations provide evidence of this association. Future large-scale clinical trials are needed to further evaluate the evidence of causality and the efficacy of antibacterial therapy for coronary artery disease.