Clopidogrel is a mainstay in the treatment of patients with acute coronary syndromes or those receiving endovascular prostheses.However,its efficacy has been challenged in the recent past by studies suggesting variable individual responsiveness and by new,more potent competitors,such as prasugrel and ticagrelor. But what is the actual body of evidence in support of clopidogrel?Is there any dark side of the moon?What is the role of prasugrel,which has already been approved in Europe and in the United States?And what will be the future role of ticagrelor,when approved for routine clinical practice?We hereby concisely summarize the scope of this clinical choice,providing arguments in favor and against each of the three antiplatelet agents:clopidogrel,prasugrel,and ticagrelor. Clopidogrel is a mainstay in the treatment of patients with acute coronary syndromes or those receiving endovascular prostheses. However, its efficacy has been challenged in the recent past by studies suggesting variable individual responsiveness and by new, more potent competitors, such as prasugrel and ticagrelor. But what is the actual body of evidence in support of clopidogrel? Is there any dark side of the moon? What is the role of prasugrel, which has already been approved in Europe and in the United States? And what will be the future role of ticagrelor, when approved for routine clinical practice? We hereby concisely summarize the scope of this clinical choice, providing arguments in favor and against each of the three antiplatelet agents: clopidogrel, prasugrel, and ticagrelor.