Major bleeding in patients taking oral anticoagulants for stroke prevention can progress to catastrophic bleeding if it is not controlled. This is especially of concern if the bleeding is related to the use of a novel oral anticoagulant (NOAC) such as dabigatran or rivaroxaban, given the dearth of literature addressing the reversal of their anticoagulant effects. The goal of treatment is to prevent progression to catastrophic hemorrhage or exsanguination, and decrease bleeding-related morbidity and mortality. Clinical decisions in such instances should be made in a timely fashion to address the necessity for intervention. Animal models have shown potential for the use of 'fresh frozen plasma (FFP) or prothrombin complex concentrate (PCC) in reversing bleeding related to novel oral anticoagulants. However, there is paucity of clinical trials assessing the efficacy of these agents in humans in such clinical scenarios. Hence, there are no guidelines or ideal agents to use in such a scenario. We do not recommend the use of FFP for bleeding related to NOACs. In the setting of early overdose of dabigatran (within 3-4 hours), activated charcoal may be given, and hemodialysis may be used if there is evidence of critical organ bleeding. In our opinion, 4-factor PCC or 3-factor PCC at a dose of about 50 U/kg may be given in an emergency setting to manage bleeding related to factor Xa inhibitors such as rivaroxaban or apixaban, but not direct thrombin inhibitors such as dabigatran. We are also of the opinion that aPCC (FEIBA®) would not be helpful for management of direct thrombin inhibitor (dabigatran)-related bleeding, based on current available efficacy data in humans. We reserve the use of Novoseven® as a last resort, given the lack of pre-clinical or clinical data supporting its ability to reverse the anticoagulant effects of NOACs, except in one case report where it was used in combination with hemodialysis.