Since the advent of percutaneous coronary intervention (PCI), intravenous unfractionated heparin has been the primary antithrombotic therapy to prevent periprocedural ischemic complications. As compared with unfractionated heparin, low molecular weight heparins (LMWHs) have a greater bioavailability and a more predictable therapeutic response. In several recent studies of patients undergoing PCI, LMWHs have been shown to be as safe and effective as unfractionated heparin; given their better pharmacokinetic profile and the lack of need for coagulation monitoring, they have the potential to replace unfractionated heparin during coronary interventions. This article reviews the current status of anticoagulation therapy with unfractionated heparin and LMWHs in the cardiac catheterization laboratory.