Intravascular fibrin deposition is believed to play an important role in the development of intimal hyperplasia, which is a hallmark of several human vascular disorders, including atherosclerosis and restenosis after balloon angioplasty. Plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor or tissue- and urinary-type plasminogen activator, plays a key role in fibrin homeostasis by controlling plasmin formation. PAI-1 may also modulate vascular pathology via alternative pathways, such as inhibiting activated protein C and altering interactions between vascular smooth muscle cells and the extracellular matrix. The diverse functional profile of PAI-1 likely accounts for the variation observed in its impact on intimal hyperplasia in different disease models. This review examines recent studies addressing the vascular function of PAI-1, and those assessing the role of fibrin as a downstream mediator of PAI-1's effects.