The antiplatelet agent clopidogrel, given alone or in addition to aspirin, is effective in reducing the composite end point of death from cardiovascular causes, nonfatal myocardial infarction, or stroke in patients with acute coronary syndromes. However, many patients receiving clopidogrel still sustain these poor outcomes. Furthermore, laboratory assays of platelet response(s) to clopidogrel show wide interindividual variability, with some patients being classified as “nonresponders” or “resistant” to clopidogrel. Understanding why these assays give such different results is essential to their possible future utility as guides to therapeutic decision-making and new drug development.