The fibrinolytic system comprises a cascade of serine proteinase activation events that culminate in the generation of plasmin and, subsequently, degradation of fibrin. Although all components of the fibrinolytic system are present at birth, plasma concentrations of key components in infants and children differ physiologically from those in adults. Until the age of 6 months, plasma concentrations of plasminogen and alpha (2)-antiplasmin are decreased to 50% and 80% of adult values, respectively, while plasma concentrations of tissue-type plasminogen activator are decreased and plasminogen activator inhibitor-1 are increased throughout childhood. In addition, the rate of plasmin generation in newborns and the overall fibrinolytic activity during childhood are decreased compared with adults. Strong evidence suggests that age-dependent differences in the fibrinolytic system critically influence the effectiveness and safety of thrombolytic agents. In addition, recent studies suggest that impaired fibrinolysis may play an important role in the pathogenesis of several diseases such as venous and arterial diseases and vasculitis, which are associated with both endothelial cell damage and increased thrombotic risk. This article will discuss the ontogenic features of the fibrinolytic system in children and summarize the available information on the effect of developmental fibrinolysis on both the course of specific disease states and the response to thrombolytic therapy in children.