Significant advances in pharmacotherapy for patients undergoing percutaneous coronary intervention (PCI) have occurred during the past decade, including the introduction and approval of new antithrombin and antiplatelet therapies, as well as modifications in dosing, administration, and/or duration of older pharmacotherapy regimens. Also, off-label (i.e., not approved by the United States Food and Drug Administration) use of certain agents has become common. Given the novel nature of these agents and the nuances of therapy, the pharmacist and other health care professionals should play an integral role in collaboration with interventional cardiologists in development of hospital protocols, determination of appropriate agent selection, assessment of patient renal function and hematologic status, dosing, and monitoring for adverse effects. In this guide, the newer antiplatelet and antithrombin drugs that may be used during PCI are reviewed, and recommendations regarding the proper administration of these agents are provided.