Anticoagulation with non-vitamin K antagonists (Non vitamin K oral anticoagulant (NOACs)) including dabigatran, rivaroxaban, apixaban and edoxaban is at least as effective as warfarin, has fewer drug and food interactions and does not require monthly monitoring. Although major bleeding with NOACs is infrequent, there remains concern about the ability to effectively treat episodes of major bleeding. New agents have been developed that are capable of providing rapid reversal of the anticoagulation effect of NOACs. Idarucizumab normalises the dilute thrombin time and the ecarin clotting time, both of which are elevated with dabigatran. Andexanet alfa reduces increased anti-factor Xa activity seen with the use of rivaroxaban and apixaban. A universal reversal agent is in development. These agents, unlike agents to reverse the anticoagulation effect of vitamin K antagonists, appear to reverse the specific NOAC anticoagulant. The development of reversal agents is a major advancement in managing bleeding in the era of NOACs. Future studies will be required to determine the impact on important clinical outcomes.