Local delivery of therapeutic agents offers promise as adjuncts during percutaneous interventions. The potential advantages of local delivery include direct delivery to the lesion site, lower doses of the agent resulting in lower costs and/or greater efficiency, and the potential for increased potency. Early trials focused primarily on the use of anti-thrombotic therapy using agents such as urokinase, heparin, and the heparinoids. These therapies, limited by an inadequate knowledge of the pharmacodynamics of the agents, had disappointing outcomes. Recent trials have focused on the use of later generation delivery devices that have improved delivery kinetics as well as agents that have improved resonance within the artery wall. It is anticipated that these new approaches will improve the clinical outcomes of local drug delivery during percutaneous interventions.