Rupture of an atherosclerotic plaque with subsequent thrombosis and myocardial ischemia is the patho-physiological mechanism in acute coronary syndromes. Tissue factor (TF) as the main initiator of the extrinsic coagulation cascade plays a central role in the pathogenesis of acute coronary syndromes. The extent of the thrombotic process is modulated by local vascular TF of the ruptured plaque as well as by circulating TF. In addition, TF alters signaling pathways and, thereby, contributes to inflammatory reactions and vascular remodeling. This review addresses current concepts of the role of TF in acute coronary syndromes and discusses potential consequences and therapeutic approaches.