Although advances during the last decade have transformed the management of coronary artery disease, deficiencies in our understanding of the basic processes of arterial thrombosis and restenosis after percutaneous intervention continue to present major challenges to their prevention. While coronary stenting has in selected cases provided the first effective approach to the problem of restenosis, new devices such as atherectomy have largely proven ineffective in this field. Similarly, despite evidence that many pharmacological agents reduce neointimal hyperplasia in experimental models, in clinical trials these agents have failed to attenuate the restenotic process. This may reflect patients' inability to tolerate the high systemic drug concentrations required to achieve adequate levels for sufficient time at the target site, necessitating a shift in the focus of therapeutic agents for the prevention of thrombosis and restenosis to local or site-specific delivery. The major advantage that local drug delivery may potentially provide is the ability to achieve high and sustained local concentrations of drug without large systemic doses, thus minimizing systemic toxicity.