The therapeutic use of thrombolytic agents is the natural result of the increasing understanding of the pathophysiologic mechanisms underlying normal and deranged thrombosis and fibrinolysis. Plasminogen activators capable of increasing the production of plasmin exhibit considerable efficacy in the treatment of a variety of arterial and venous thrombotic disorders. The ideal thrombolytic agent has yet to be developed but the desired clinical result of rapid opening of the thrombosed vessel without reocclusion, without activation of systemic fibrinogenolysis, and without a risk of hemorrhage is well defined. Clinical studies clearly demonstrate that the addition of a variety of adjunctive agents to the available thrombolytics enhances benefit without inordinate risk. The addition of intravascular angioplasty and stenting to thrombolysis increases the potential long-term benefit. Newer thrombolytic agents and new protocols for the use of existing therapies offer the promise of saving many who would otherwise succumb to coronary or cerebral arterial thrombosis or to venous thromboembolism.