Coronary angioplasty has become a successful and widely used treatment for patients with coronary artery disease since its first clinical application in 1977. The primary success rate has improved despite the increase in procedure and case complexity. However, acute reocclusion and late restenosis, which constitute the most important problems after successful angioplasty, continue to occur in about 5% and 35% of patients within 3 to 6 months, respectively. Angioscopic and pathologic observations have suggested that a multifactorial pathophysiologic process accounts for acute reocclusion, involving marked thrombosis, intimal dissection, medial and subintimal hemorrhage, vascular recoil and vasocontriction. In contrast, chronic restenosis involves the development of fibrocellular intimal hyperplasia within a milieu created by vascular injury, platelet activation, thrombin generation and the release of mitogens. Although current pharmacologic approaches, which involve antithrombotic and anticoagulant therapy, have been largely ineffective in eliminating acute reocclusion and chronic restenosis, recent advances in the research in thrombosis, platelet receptors and smooth muscle growth regulation have allowed new therapeutic options to be tested in the experimental setting, with subsequent potential clinical applications in patients.