Fibrinolysis is a process that prevents blood clots from growing and becoming problematic. Systemic or local thrombolysis may be an option for arterial occlusions distal to the popliteal artery (thrombectomy is the usual therapeutic approach for occlusion of less than 24 h duration proximal to this site). Intravenous streptokinase will lyse 80% of occlusions if infusion begins within 12 h, and 60% if it is delayed for up to 3 days. Physiologic thrombolysis is efficient, while pathologic aberrations in the fibrinolytic system may result in either thrombotic or hemorrhagic disease. This review considers the molecular interactions involved in fibrinolysis, discusses the normal control mechanisms that provide for localized activation without systemic effects, and describes the molecular mechanism of plasmic degradation of fibrinogen and of cross-linked fibrin. The consequences of excessive or deficient fibrinolysis are discussed and specific examples cited of pathologic hemostasis directly related to abnormalities in the fibrinolytic system. Physiologic thrombolysis is efficient, while pathologic aberrations in the fibrinolytic system may result in either thrombotic or hemorrhagic disease. This review considers the molecular interactions involved in fibrinolysis, discusses the normal control mechanisms that provide for localized activation without systemic effects, and describes the molecular mechanism of plasmic degradation of fibrinogen and of cross-linked fibrin. The consequences of excessive or deficient fibrinolysis are discussed and specific examples cited of pathologic hemostasis directly related to abnormalities in the fibrinolytic system.