Platelet adhesion, activation and aggregation are central to the pathophysiology of the acute coronary syndromes. Clopidogrel, an oral thienopyridine derivative, is a platelet adenosine diphosphate receptor antagonist capable of inhibiting platelet activation. During the last decade, the utility of clopidogrel has been evaluated in several common clinical scenarios in a large number of patients. The benefits of clopidogrel in patients with stable coronary artery disease undergoing elective percutaneous coronary interventions and in patients presenting with acute coronary syndromes are now well established. This review outlines the pharmacology of clopidogrel, highlights the results of clopidogrel trials in the setting of acute coronary syndromes, and presents areas of uncertainty and potential future work.