Antagonists of the platelet receptor glycoprotein (GP) IIb-IIIa are a novel class of antithrombotic agents that provide more comprehensive platelet blockade than the combination of aspirin and heparin. Studies in patients scheduled for percutaneous coronary intervention and those with unstable angina or non–Q-wave myocardial infarction have shown that a combination of intravenous GP IIb-IIIa inhibitors with aspirin and heparin is associated with a reduction in death or myocardial infarction compared with therapy with aspirin and heparin alone. As with other antithrombotic agents, the principal safety issue with GP IIb-IIIa inhibitors is bleeding, because the potent antiplatelet effect of these drugs may adversely affect hemostasis. Increased risk of hemorrhage is of particular concern for patients who subsequently require emergency or urgent bypass surgery because the rate of bleeding complications in these patients is considerable even in the absence of prior GP IIb-IIIa therapy. Additionally, antagonists of GP IIb-IIIa may increase the risk of thrombocytopenia. The safety profiles of various GP IIb-IIIa inhibitors are largely a function of their pharmacokinetic and pharmacodynamic properties, most notably the reversibility of platelet inhibition and the rate of plasma clearance. Knowledge of the pharmacokinetic and pharmacodynamic properties of the GP IIb-IIIa inhibitors is critical for the appropriate utilization of this new class of drugs. (Am Heart J 1999;138:S263-S275.)