Hypofibrinolysis, leading to the decreased removal of fibrin deposits and the breakdown of extracellular matrix, is a candidate for a role in the development of atherothrombosis. Reduced plasma fibrinolysis is mainly attributed to an increased plasminogen activator inhibitor (PAI)-1 level, which is considered to be a biological risk factor for coronary heart disease. Increased plasma PAI-1 levels are related to the insulin resistance syndrome and could partly explain the role of this metabolic syndrome in the development of atherothrombosis. Increased PAI-1 expression has been described in atherosclerotic lesions. Lipoprotein (a) [Lp(a)] also accumulates in the damaged vessel wall. The atherogenic effect of Lp(a) could partly be explained by its interaction with the fibrinolytic system through apolipoprotein (a), which presents a strong homology with plasminogen. Contributions of systemic and local disturbances of PAI-1 and Lp(a) expression in atherothrombosis have been reported.