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Reperfusion therapy using thrombolytic agents has been shown to be a safe and effective treatment strategy for arterial ischemia, venous thrombosis, massive pulmonary embolism, and acute stroke. Thrombolytic agents have evolved over the course of a few decades, from nonfibrin selective to fibrin-selective agents. The development and modification of these agents have resulted in improved understanding of their pharmacologic attributes, and their effects on the complex molecular events that occur during thrombolysis goal-directed therapies. The current review focuses on the physiology and pharmacology of the thrombolytic agents that have been or are currently in use for interventional thrombolysis interventions. Attention is also given to the particular role that thrombolytic agents play in the current management of peripheral vascular disease and acute stroke. [ABSTRACT FROM AUTHOR]