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The incidence of patients with trauma on novel oral anticoagulants (NOACs) for the treatment of thromboembolic disorders is increasing. In severe bleeding or hemorrhage into critical spaces, urgent reversal of this underlying pharmacologic coagulopathy becomes paramount. Optimal reversal strategy for commonly used NOACs is still evolving. Basic tenets of evaluation of patients with trauma and resuscitation remain the same. Clinical outcomes data in bleeding human patients with trauma are lacking, but are needed to establish efficacy and safety in these treatments. This article summarizes the available evidence and provides the optimal reversal strategy for bleeding patients with trauma on NOACs.