The interaction between the vulnerable atherosclerotic plaque and thrombus formation, a process referred to as atherothrombosis, is the cornerstone of acute coronary syndromes. Advances in noninvasive imaging have helped to identify novel approaches to plaque stabilization, with the potential to prevent plaque rupture, including lifestyle modification and dietary adjustments, as well as pharmacologic interventions such as statins. Following an acute coronary event, strategies combining mechanical and pharmacologic therapies provide considerable advances in prevention of subsequent cardiac events. Pharmacologic strategies to prevent and treat thrombotic complications related to acute coronary syndromes have been developed to dissolve preformed thrombi and to inhibit thrombogenesis. These regimens focus on inhibiting thrombin, preventing thrombi generation, blocking the initiation of coagulation, inhibiting platelet activation, and increasing fibrinolysis.