Therapy of atherosclerotic vascular disease and neointimal hyperplasia after percutaneous interventions remain enigmatic. Despite new interventional devices, we have not altered the underlying pathological process. New devices are under development that offer the opportunity to deliver high concentrations of therapeutic agents directly to the diseased segment. The devices fall into three major mechanisms of delivery (1) diffusion, (2) infusion under pressure and (3) mechanical delivery. Diffusion catheters are atraumatic but require prolonged exposures in excess of 20 min while the pressurized infusion and mechanical catheters are more traumatic. Additionally, each system will need to be characterized with respect to efficiency of delivery with each agent used. The clinical opportunity for site-specific treatment of vascular disease is rapidly approaching. In the near future we will be able to open a narrowed vessel and also apply some agent into the lesion to facilitate healing.