Clopidogrel use is associated with a significant decrease in major adverse cardiac events when used in patients with non–ST elevation acute coronary syndromes (NSTE-ACS), and guidelines give a class I level of evidence A recommendation for the use of clopidogrel in these patients. The optimal timing of clopidogrel use has not been conclusively determined, but nearly all data available support early use in patients with NSTE-ACS. Despite this, clopidogrel usage is far less than expected based on current guidelines because of concern for bleeding at the time of possible subsequent coronary artery bypass grafting (CABG). Clopidogrel use has been associated with increased perioperative bleeding at the time of CABG, but data are mixed. Numerous studies have conclusively shown that this bleeding risk is confined to those patients receiving clopidogrel within 5 days of CABG. The absolute number of patients exposed to this possible bleeding risk is very small relative to the >1 million patients who present annually with NSTE-ACS and is estimated to be <0.8% of these patients. Recent data have shown that (1) holding clopidogrel for 5 days before CABG is safe in patients with NSTE-ACS and (2) clopidogrel use in patients with NSTE-ACS decreases ischemic events in patients referred for CABG compared to patients who are not given clopidogrel. These data strongly challenge the notion that clopidogrel should be withheld until it is determined if the patient will be referred for CABG.