Most of the serious clinical manifestations (such as unstable angina, acute MI, and many cases of sudden death) of coronary atherosclerosis result from thrombosis, usually occurring on a disrupted atherosclerotic plaque. Plaques prone to disruption have large lipid-rich cores with evidence of cap-thinning and active inflammation. Inflammatory cells may contribute to both plaque disruption and subsequent thrombosis. Here we review the evidence for the involvement of inflammation in plaque disruption and thrombosis and the potential clinical implications of this pathophysiologic paradigm.