Both clopidogrel and aspirin have been shown to decrease the rate of cardiovascular events and especially stent thrombosis in patients undergoing percutaneous coronary intervention (PCI). However, recent studies have suggested that there is large inter-individual response variability to these drugs (especially to clopidogrel) and that improved inhibition of platelet reactivity using higher doses or new, more potent agents would further reduce the occurrence of cardiovascular events, but may also increase the risk of bleeding. Many different protocols of antiplatelet therapy have been studied and have shown benefit in reducing the rate of major adverse cardiovascular events after PCI. Therefore, the choice of an appropriate antiplatelet therapy protocol is sometimes difficult for the clinician and should be individualized as per the particular patient risk, accounting for both the risk of recurrent cardiovascular events and bleeding. We review the recent data on efficacy and safety of dosing strategies for antiplatelet therapy in PCI.