The role played by glycoprotein (GP) IIb/IIIa inhibitors has continuously evolved from the initial introduction in mid 90 s until the most recent guidelines for treating acute coronary syndromes, and competed with a wider use of ADP inhibitors and novel anticoagulant drugs, to the extent that they stepped down from class I to class II recommendation in the routine setting of acute coronary syndromes. As a consequence, GP IIb/IIIa use was greatly narrowed. The purpose of this review is to define the roles that GP IIb/IIIa inhibitors may still have in acute ischemic settings by explaining why in high risk patients they might be preferable and/or whether they might be added to ADP inhibitors also emphasizing the underlying mechanistic actions. It is concluded that there might be a more extensive use of GP IIb/IIIa inhibitors in patients presenting with acute coronary syndromes, strictly based on the definition for a high risk procedure: complexity, angiographic characteristics and patient's risk profile, regardless whether STEMI or NSTEMI. The positive elements one should appreciate in GP IIb/IIIa inhibitors are: efficacy, rapid onset and reversibility of action, absence of pharmacogenomic variability, pharmacoeconomic considerations and the possibility of intracoronary administration.