The modern treatment of cardiopulmonary disease is increasingly predicated on the goal of dissolving the offending clot to establish vascular patency as rapidly as possible and then preventing rethrombosis. The availability of thrombolytic agents has made this therapeutic approach possible and the adjunctive use of heparin, coumarin, and aspirin has increased the efficacy of lytic drugs. The administration of any of these medications is associated with inherent risks, which are enhanced when they are used concomitantly. An understanding of coagulation and an appreciation of the pathophysiologic processes of the thrombotic events occurring in cardiopulmonary disease states are critical to the formulation of innovative therapeutic regimens that maximize efficacy and safety. Furthermore, knowledge of the comparative pharmacology of the various thrombolytic agents is useful in explaining the benefits and complications observed in clinical trials.