Plasminogen activator inhibitor type-1 (PAI-1) is a rapid inhibitor of tissue plasminogen activator (tPA) in circulation. Evidence suggests that the PAI-1 concentration is responsible for the regulation of the endogenous fibrinolytic system through its tPA/PAI-1 interactions. Accordingly, increased levels of PAI-1 have emerged as a masker for an increased thrombolic risk. This article represents a status report of mechanism of action, regulation of plasma levels, as well as the role of PAI-1 in arterial and venous thromboembolic disease.