Platelet inhibition is essential in the management of coronary artery disease. The American College of Cardiology/American Heart Association and the European Society of Cardiology have developed guidelines for the management of antiplatelet therapy in acute coronary syndrome and in stable coronary artery disease. In this chapter, we review the evidence for (1) P2Y12 inhibitor selection, (2) de-escalation of antiplatelet therapy, and (3) platelet function and genotype testing. Thereafter, we will discuss and review the available clinical practice guidelines and compare them to the evidence-base that has been generated by large randomized clinical trials.