Despite extensive data supporting their use for non-ST–segment elevation acute coronary syndromes, glycoprotein (GP) IIb/IIIa antagonists are underutilized. This is likely the consequence of confusion as to which patients should receive these agents, as well as to the most appropriate timing and venue for their initiation. We will review the advances in the understanding of GP IIb/IIIa antagonist therapy, emphasizing methods of identifying those most likely to benefit from the use of GP IIb/IIIa receptor blockade. In addition, we will consider appropriate methods/venues for use of GP IIb/IIIa receptor antagonism, including its role in an “early invasive” catheterization strategy.