This chapter discusses catheter-directed intra-arterial thrombolytic therapy. Catheter-directed intra-arterial thrombolytic therapy (CDTT) has been developed and perfected to treat thrombotic occlusion of the peripheral arteries. CDTT consists of direct intra-arterial infusion of a concentrated dose of fibrinolytic agents into the thrombus to restore blood flow to the ischemic limb. This uncovers underlying stenotic lesions which are then treated by an endovascular or surgical approach. This chapter discusses general goals of catheter-directed intra-arterial thrombolysis, thrombolytic agents, streptokinase, urokinase, recombinant tissue plasminogen activator (RTPA), clinical indications of CDTT, and contraindications of CDTT, a technique used for CDTT, monitoring the therapy, delivery catheter systems and complications of CDTT.