Clopidogrel is an effective antiplatelet drug for preventing cardiovascular events and death but also increases the risk of bleeding. There is emerging evidence that bleeding is associated with an increased risk of recurrent ischaemic events and death, even when the bleeding is not severe enough to be considered life-threatening. Reducing the risk of bleeding has the potential to improve clinical outcomes, but it is important to ensure that strategies aimed at reducing the risk of bleeding do not compromise the net clinical benefit of clopidogrel that has been demonstrated in clinical trials. Possible strategies to reduce the risk of bleeding during clopidogrel treatment include appropriate dosing of concomitant antithrombotic drugs and their avoidance unless they are of proven benefit, careful selection of patient for invasive procedures, and discontinuation of clopidogrel at least 5 days prior to coronary artery bypass graft surgery, except in unstable or very high risk patients. Management of bleeding in patients treated with clopidogrel may include temporary discontinuation of antithrombotic drugs, resuscitation with intravenous fluid, packed red cell transfusion, and surgical or other procedures to control the bleeding. The only way to overcome the antiplatelet effect of clopidogrel is with platelet transfusions because clopidogrel irreversibly inhibits platelet function for the life of the platelet, and there is no known antidote. Future research efforts should be directed towards establishing whether or not the association between bleeding and recurrent ischaemic events and death is causal and to determine the mechanism(s) responsible for the association.