Thrombosis superimposed on a disrupted plaque is the proximate event that triggers most acute ischemic syndromes and episodes of sudden cardiac death. A significant number of acute ischemic events occur in individuals without traditional atherosclerosisrelated risk factors. In an attempt to pinpoint additional risk factors, researchers are examining the thrombotic cascade and the cellular components, plasma proteins, and endothelium-derived mediators, as well as their genetic polymorphisms, that may affect this system. This article enumerates a number of potential hemostatic risk factors and discusses the evidence linking them to atherothrombotic events.