Stent thrombosis is the major cause of early adverse events during percutaneous coronary intervention. Its incidence has fallen considerably in recent years, principally due to the introduction of effective antithrombotic therapies. The selection of an appropriate antithrombotic regimen is critical in achieving a balance between reducing ischaemic events and minimising bleeding complications in patients undergoing percutaneous coronary intervention. In this article, evidence for the role of antiplatelet and anticoagulant therapies is discussed, including the thienopyridines, glycoprotein IIb/IIIa receptor antagonists, direct thrombin inhibitors and pentasaccharides.