Direct oral anticoagulants are increasingly used in clinical practice and have addressed many of the issues related to vitamin K antagonists. However, the lack of reversal in life-threatening situations raises concerns regarding patient safety. Thus, current research is aimed at developing reversal agents that can safely neutralize the effects of anticoagulants. We present the design and mechanisms of action of and the animal models, clinical trials, and current evidence supporting the use of these emerging reversal agents. Idarucizumab is approved in many countries, and andexanet alfa has been approved by the US FDA, whereas others are in clinical trials. In view of the results of clinical studies to date, the problems of safety, price and accessibility remain. Therefore, these antidotes are a significant step towards improving the field of urgent and emergency reversal. From a practical perspective, post-market surveillance will be crucial to monitor the safety and effectiveness of these agents.