Patients treated with anticoagulants have an unavoidable risk of bleeding complications. There are, for all oral anticoagulants, several potential options for management of major bleeding. The first action is to assess the causative role of the anticoagulant in the current bleeding. Supportive measures have been assessed in several post hoc analyses of the phase III pivotal trials with the non–vitamin K antagonist oral anticoagulants (NOACs). Those results will be reviewed here together with emerging data on the efficacy and safety of the specific antidotes idarucizumab (for dabigatran) and andexanet-α (for factor Xa inhibitors). Regular or activated prothrombin complex concentrates are also evaluated and might have a role as alternatives for management of NOAC-associated major bleeding if the “specific” antidote is not available. Once hemostasis has been achieved, it is imperative to assess the possibility and timing of resumption of anticoagulation, as these patients have an inherent prothrombotic state and a non-negligible proportion of patients will have thromboembolic complications during the first month after the hemorrhage. Many factors will have to be taken into account for this decision and unfortunately the guidelines in this respect are very weak if at all available. This review will hopefully provide some assistance in the management of major bleeding and posthemorrhage care.