A lack of consensus on anticoagulant reversal during acute trauma is compounded by an aging population and the expanding spectrum of new anticoagulation agents. Developments in laboratory assays and transfusion medicine, including thromboelastography, recombinant factors, and factor concentrates, have revolutionized care for anticoagulated trauma patients. Accordingly, clinicians must be fully aware of drug mechanisms, assays to determine drug activity, and appropriate reversal strategies for patients on anticoagulants. Drugs include vitamin K antagonists, direct thrombin inhibitors, direct factor Xa inhibitors, low molecular weight heparin, and antiplatelet agents. This article discusses the appropriate assessment and management of trauma patients receiving these agents.