Antiplatelet agents are the cornerstone of treatment for patients with acute coronary syndromes and patients undergoing percutaneous coronary intervention. The current "gold standard" consists of a combination of aspirin and clopidogrel administered orally shortly before invasive procedures and then continued in the form of maintenance doses. Not all patients respond optimally to standard therapy. Resistance to the antiplatelet activity of both drugs when used either singly or in combination has been observed and may lead to treatment failure, including further atherothrombotic events. Potential limitations associated with the combined use of aspirin and clopidogrel have inspired clinical investigation into several promising new antiplatelet agents as potential additions or alternatives to standard therapy. The candidates include prasugrel, which has a mechanism similar to that of clopidogrel but with superior pharmacokinetics; ticagrelor, a nonthienopyridine that binds reversibly to the platelet P2Y(12) receptor; cangrelor, an intravenously administered analogue of ticagrelor; and various thrombin receptor antagonists.