Aggressive intravenous and oral dual antiplatelet therapy has established primary percutaneous coronary intervention (PCI) as the standard of care for acute myocardial infarction. Clopidogrel is currently the thienopyridine of choice for dual antiplatelet therapy in patients treated with PCI. The dose regime and duration of therapy of clopidogrel has undergone multiple refinements. Recently, 2 novel third generation oral inhibitors of P2Y12 receptors, prasugrel and ticagrelor, have undergone clinical evaluation with promising results. This article is a non-exhaustive review of the literature, concentrating on the role of current and novel oral antiplatelet agents for acute myocardial infarction particularly highlighting the limitations and issues associated with clopidogrel use.