In this review we discuss the association of overall hypofibrinolysis and individual fibrinolytic protein levels with venous and arterial thrombosis. Decreased overall fibrinolytic potential and high plasma levels of thrombin-activatable fibrinolysis inhibitor have been consistently associated with risk of venous thrombosis, whereas little evidence exists for a role of plasminogen, α2-antiplasmin, tissue plasminogen activator, and plasminogen activator inhibitor 1. Overall fibrinolytic potential has been associated with arterial thrombosis in young individuals, but studies on the individual components gave conflicting results. These inconsistent results could be a consequence of nonfibrinolytic properties of fibrinolytic proteins, including roles in inflammation, vascular remodeling, atherosclerosis, and the metabolic syndrome. The nonfibrinolytic properties of these proteins may have opposing effects on development of arterial disease as compared with the lytic properties, which may explain opposite results in different studies with slightly different population characteristics. These properties may be more relevant in arterial than in venous thrombosis.