Antagonists of platelet glycoprotein IIb/IIIa (abciximab, tirofiban, eptifibatide) have now an approved role in reducing the extent of thrombotic complications leading to myocardial damage during percutaneous coronary interventions (PCI). This effect likely here translates into a long-term survival benefit. However, the question of their usefulness in different clinical scenarios (stable or unstable coronary disease, without PCI) has not been fully answered on the basis of considerations of dosing and cost-effectiveness. These agents seem most useful in high-risk patients with unstable coronary syndromes especially in the presence of co-morbidities such as diabetes or renal insufficiency. This article summarizes reasons for the ongoing debate on their efficacy and highlights areas of uncertainty.