Clopidogrel has demonstrated improved outcomes for patients with acute coronary syndromes in several large randomized controlled trials. However, some questions exist about the use of clopidogrel in practice. Who benefits from clopidogrel? When should clopidogrel treatment be initiated? How much clopidogrel should be administered and for how long? Reviewing the results from trials completed to date that have assessed clopidogrel in patients with acute coronary syndromes may help to answer some of these questions. Clinical trial results have demonstrated a reduction in the composite endpoint of death, myocardial infarction, or stroke for patients with acute coronary syndromes who received clopidogrel plus aspirin compared with aspirin alone. For this patient population, early treatment with clopidogrel more than 6 hours before percutaneous coronary intervention (PCI) was associated with a reduction in the risk of death or recurrent ischemic events. The benefits of initiating patients on a 600-mg loading dose of clopidogrel before PCI have been demonstrated in several clinical trials. Clinical trial results and current guidelines recommend long-term treatment with clopidogrel for up to 1 year after PCI.