In general terms, thrombotic disorders of the cardiovascular system are characterized by poorly regulated, nonphysiologic thrombus formation. Considered more specifically, however, pathologic thrombosis represents a critical imbalance, frequently at both the systemic and vascular levels, of coagulation, anticoagulation and fibrinolysis. Indeed, the balance is shifted toward coagulation, preventing normal physiologic blood flow. Anticoagulants have been a mainstay in the treatment of thrombotic disorders. However, emerging strategies have focused primarily on thrombus dissolution (fibrinolysis), which can be efficiently achieved with the administration of extrinsic plasminogen activators. Clearly, thrombolytic therapy is currently the most direct means of restoring blood flow, vital organ perfusion and hemostatic balance among patients with thrombotic disorders of the cardiovascular system.