Antiplatelet treatment in patients with an acute coronary syndrome (ACS), without or with ST segment elevation myocardial infarction (STEMI), forces to keep the balance between potential threats and optimal clinical advantages. Apart from clopidogrel, glycoprotein (GP) IIb/IIIa inhibitors (abciximab and 2 small molecules, tirofiban and eptifibatide) have come to the clinical scene. Recent evidence (2009–2011) is reviewed pointing to pharmacoeconometric considerations of concern in times of budget restrictions worldwide. In ACS, when clopidogrel plus aspirin are on, there might be no advantage to add small molecules. Whereas in STEMI patients treated by primary PCI, all 3 GP IIb/IIIa antagonists might be superimposable, when only ACS is present and PCI is elective, definite distinction among the 3 agents, both pharmacoeconomically and pharmacodynamically, might be invoked. There are still points open to debate. Among these the route (upstream versus downstream) is still a matter of uncertainties. Moreover, theoretically, there might be differences not only between abciximab and small molecules (mostly superimposable) but also between tirofiban and eptifibatide (the former being potentially more potent). Thus, a long way is needed before a prominent agent among GPIIb/IIIa inhibitors may be selected. The game is still open, a role will be played soon by new agents.