This article discusses platelet active drugs as part of the Seventh American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines. New data on antiplatelet agents include the following: (1) the role of aspirin in primary prevention has been the subject of recommendations based on the assessment of cardiovascular risk; (2) an increasing number of reports suggest a substantial interindividual variability in the response to antiplatelet agents, and various phenomena of "resistance" to the antiplatelet effects of aspirin and clopidogrel; (3) the benefit/risk profile of currently available glycoprotein IIb/IIIa antagonists is substantially uncertain for patients with acute coronary syndromes who are not routinely scheduled for early revascularization; (4) there is an expanding role for the combination of aspirin and clopidogrel in the long-term management of high-risk patients; and (5) the cardiovascular effects of selective and nonselective cyclooxygenase-2 inhibitors have been the subject of increasing attention.