Platelet aggregation is a crucial feature in coronary artery thrombus formation and is a major causative factor in both acute coronary syndromes (ACS) and reocclusion after percutaneous coronary interventions (PCI). The glycoprotein (GP) IIb/IIIa (αIIbβ3) integrin receptor is the pivotal mediator of platelet aggregation. In late 1990s, the introduction of GP IIb/IIIa inhibitors (GPI) was associated with a reduction of ischemic complication, and a clear clinical benefit in PCI during ACS, for both non ST-elevation (NSTE) and ST-segment elevation myocardial infarction (STEMI). The currently available GPI (abciximab, eptifibatide and tirofiban) tended to be replaced in the current therapy of STEMI by different agents and this is in part related to the effectiveness and to the potential adverse effects (thrombocytopenia and bleeding). There might be a certain level of variability among these agents and here we have reviewed only abciximab in detail. Interestingly, however, the story may not be entirely different from that of positive inotropic agents in the context of acute ischemia where the potent action to sustain left ventricular function had an arrhythmogenic counterpart to evaluate and take into consideration and therefore therapeutically it will always be necessary to weigh benefits and harms if actions are expected by relatively potent agents.