Although coronary angioplasty has been in clinical use for only 15 years, continued refinements in technique, instrumentation, and adjunctive therapy have led to high initial success rates despite broader patient selection and the increasing complexity of lesions attempted. Antiplatelet therapy in the form of 80 to 325 mg of aspirin begun before the procedure has been demonstrated to be of benefit in decreasing the acute complication rate associated with PTCA. In the future, this beneficial effect may be augmented by the addition of monoclonal antibody inhibitors to platelet membrane glycoprotein IIB/IIIa, possibly at the expense of a mild-to-moderate increase in bleeding complications. Although routine prolonged antithrombotic therapy has not been useful after uncomplicated angioplasty, there is evidence that antithrombotic therapy with heparin for 1 or more days before angioplasty will benefit patients with unstable angina or evidence of thrombus on angiography. Although patients with thrombus or coronary dissection after the procedure probably also benefit from extended heparin therapy, most trials have specifically excluded these patients from study. More potent and specific antithrombin and antiplatelet agents are currently being investigated in human trials and may further lower acute complication rates. Although platelets, thrombin, and mural thrombosis have all been implicated as factors in restenosis, the process itself remains incompletely understood, and no therapy has been shown to be of benefit in humans. The specific platelet IIb/IIIa inhibitors, hirudin, hirulog, and factor Xa inhibitors have all shown promise in animal models of restenosis, and ongoing or planned trials will define their efficacy in humans.