Target-specific oral anticoagulants (TSOACs) that directly inhibit thrombin (dabigatran) or factor Xa (rivaroxaban, apixaban) are effective and safe alternatives to vitamin K antagonists (VKAs) and low-molecular-weight heparin (LMWH). Although these agents have practical advantages compared with VKAs and LMWH, there are no antidotes that reverse their anticoagulant effect. Clinical evidence for the efficacy of nonspecific therapies that promote formation of fibrin (prothrombin complex concentrate [PCC], activated PCC [aPCC], and recombinant factor VIIa) in the setting of TSOAC-associated bleeding is lacking, and these prohemostatic products are associated with a risk of thrombosis. In the absence of specific antidotes, addition of PCC or aPCC to maximum supportive therapy may be reasonable for patients with severe or life-threatening TSOAC-associated bleeding. Targeted antidotes for these agents are in development.