The treatment of patients with acute coronary syndromes has changed dramatically over the last several years. Most patients now undergo some form of percutaneous coronary intervention (PCI), which includes either stent placement or percutaneous transluminal coronary angioplasty (PTCA). Along with new medical interventions for acute coronary syndromes comes the need for new antithrombotic therapies. Combination therapy with antiplatelet agents (aspirin, adenosine diphosphate inhibitors), glycoprotein (GP) IIb-IIIa receptor inhibitors, and anticoagulants (unfractionated heparin or low-molecular-weight heparins) is administered, depending on the type of intervention and severity of the coronary lesion. Bivalirudin is a direct thrombin inhibitor that recently was approved as an alternative to heparin in patients undergoing PTCA. Compared with unfractionated heparin, bivalirudin reduces the rate of death, myocardial infarction, or revascularization, with a concurrent reduction in bleeding. This agent offers promise as a replacement for unfractionated heparin in PCI and is being studied in comparison with unfractionated heparin plus GP IIb-IIIa receptor inhibitors in patients undergoing intracoronary stent placement.