The use of intra-arterial thrombolytic therapy is well established for both native arteries and bypass grafts. Despite extensive experience, significant areas of controversy remain, including 1) appropriate indications, 2) the efficacy and dosing of fibrinolytic agents, 3) risks, and 4) cost effectiveness. This review provides an overview of current developments in the use of fibrinolytic agents, as well addressing the issues of patient selection, choice of lytic agent, patency results, adverse effects and risks, along with cost considerations and future directions.