Inflammatory process plays a fundamental role in ischemic coronary artery disease (CAD) in terms of both the etiology of atherosclerosis and the pathophysiology of CAD. In particular, chronic inflammation plays a key role in coronary artery plaque instability and subsequent occlusive thrombosis. It is therefore important to clarify the mechanism underlying the activation of the immune response in the pathogenesis of CAD. Currently 10 toll-like receptors (TLRs) have been reported in mammalian species, and these appear to recognize distinct pathogen-associated molecular patterns controlling innate immune responses. In recent studies, signaling of two forms of human TLR (TLR2 and TLR4) has been shown to be involved in the pathogenesis of CAD, establishing a key link between the progression of coronary atherosclerosis and immune response to both foreign pathogens and endogenously generated inflammatory ligands. A better understanding of TLR signal may provide a novel therapeutic agent for the treatment of CAD. This review summarizes the relationship between the pathogenesis of ischemic coronary artery disease and the human TLR system.