The chapter provides information on triple antiplatelet therapy especially with intravenous glycoprotein IIb/IIIa blockers, came with great expectations, as an important adjuvant in the antiplatelet regimens for PCI in the management of ACS to reduce acute occlusions. The chapter also mentions on antiplatelet agents such as acetyl salicylic acid (aspirin), a cyclooxygenase inhibitor via blocking thromboxane A2 receptor, Ticlopidine was the first agent working on platelets via alternative adenosine diphosphate (ADP) receptor pathway. Prasugrel, another thienopyridine derivative mediated via an ADP receptor, showed 19% relative risk reduction. Clopidogrel, (TRITON-therapeutic outcomes by OPTIMIZING platelet Inhibition; Eptifibatide, a synthetic, cyclic heptapeptide that mimics arginine-glycine-aspartic acid (RGD) sequence is capable of competing fibrin link on glycoprotein IIb/IIIa receptors on the platelet surface. Finally the chapter concludes with the remarks as Now glycoprotein IIb/IIIa blockers cannot be justified in each and every patient of ACS, their use is acceptable in selected high-risk patients only that too limited in the cardiac catheterization laboratory during PCI. Upstream usage in selected patients only prior to transfer to a primary PCI center has been recommended.