The initiation, modulation and resolution of thrombus associated with eroded or unstable coronary plaques are critical determinants of acute coronary events. This itself is dependent on the cellular function of the surrounding endothelium and vascular wall. In particular, the regulation of vascular tone and the acute release of tissue plasminogen activator by the endothelium make important contributions to the defence against intravascular thrombosis. These aspects of endothelial function may provide major new insights into the pathophysiology of cardiovascular disease, and to shape future therapeutic interventions.