The fibrinolytic system is important in thrombus resolution at the site of atherosclerotic plaque rupture. The usual levels of plasma fibrinolytic factors have been hypothesized to be important in predicting atherothrombotic events. In this report, prospective clinical, prospective epidemiological, and genetic epidemiological studies of fibrinolytic factors and incident cardiovascular disease are reviewed. Many prospective studies have reported an unadjusted positive association between plasma fibrinolytic markers (eg, tissue plasminogen activator antigen or plasminogen activator inhibitor antigen) and risk of cardiovascular disease. The association tends to be strong and demonstrate a dose-response, but often becomes statistically nonsignificant after adjustment for other risk factors. About half of the genetic epidemiological studies suggest that a polymorphism of a gene coding for fibrinolysis may be associated with cardiovascular disease, but that the relative risk is modest, at best. Thus, epidemiological evidence to date is inconclusive about whether impaired fibrinolysis may be a 'cause' of atherothrombotic events. In fact, alterations of plasma fibrinolytic factors might be a 'consequence' of atherosclerosis. At present, it seems premature to recommend routine measurement of fibrinolytic factors to identify patients at risk of cardiovascular disease events. Some directions for future research on this topic are offered.