Anticoagulation therapies are 1 of the most commonly encountered therapeutic areas by health care professionals each day. One of the most important adverse effects of anticoagulation therapy is life-threatening hemorrhage, and it may result in visits to the emergency department. Some of the common reversal agents include Vitamin K, protamine sulfate, desmopressin, recombinant Factor VIIa, and prothrombin complex concentrates. Each of these agents has the potential to reverse specific anticoagulation therapies, but each agent has a unique administration procedure and monitoring parameters. However, these agents are not without risk of adverse effects. Knowledge of unique aspects of each reversal agent and the anticoagulation therapy must be considered when selecting or recommending pharmacologic anticoagulation reversal therapy. The intent of this review is to discuss the relevant management issues associated with anticoagulant reversal in the emergency department.