Thrombus dissolution is dependent on activators of plasminogen, the principal enzyme of fibrinolysis, reaching plasminogen bound to the surface of fibrin, and overcoming the many inhibitors of clot lysis present in the plasma milieu. In dialysis patients with occluded catheters and grafts, three activators — streptokinase, urokinase, and tissue plasminogen activator (tPA) — have been used. Streptokinase has fallen out of favor because of its adverse effect profile; urokinase has been the mainstay of therapy. Urokinase has been used alone and in conjunction with mechanical methods for clearance of thrombi from arteriovenous grafts. It has also been instilled into occluded central venous catheters, but often is more effective if given systemically during dialysis in order to lyse the fibrin sheath that surrounds the catheter tip. Due of manufacturing problems, urokinase is no longer available and management with tPA is being actively investigated. One small trial showed that recombinant tPA was significantly more effective than urokinase for restoring catheter patency, but the drug is not yet approved for this purpose by the FDA, and current packaging is not optimal. The problems with thrombolytic agents may be obviated in the future by better methods of prevention of thrombus formation, monitoring flow to anticipate occlusion, and early mechanical interventions to restore patency.