The contribution of platelets in the pathophysiology of thromboses has established antiplatelet therapy as a cornerstone for prevention or treatment of these disorders. However, patients on antiplatelet drugs undergoing surgery face the life-threatening dilemma between the risk of perioperative thrombosis by ceasing therapy and restoring platelet function versus the risk of surgical bleeding by its continuation. According to their mechanism of action, antiplatelet drugs can be conventionally classified as agents that inhibit cyclooxygenase, block the platelet adenosine diphosphate P2Y12 receptor, inhibit phosphodiesterase, or block platelet glycoprotein IIb/IIIa. Although several tests have been developed to assess platelet inhibition by most of these compounds, studies to date have not been able to reliably evaluate the diagnostic efficiency of these tests to predict hemorrhage and/or blood loss, and accordingly perioperative assessment of drug-induced platelet inhibition cannot be recommended as yet. Although several management options are available to counteract the hemorrhagic risk of surgical patients using antiplatelet agents, perioperative discontinuation of these drugs is the preferable choice wherever possible. The use of platelet transfusions should be limited where necessary to the treatment of major, life-threatening bleeding. The contribution of newer hemostatic agents, such as desmopressin and recombinant activated factor VII, is yet to be fully determined, and there remain many challenges and unresolved issues in the clinical care of these patients.