Over-anticoagulation is a common problem with warfarin therapy and can lead to major or life-threatening bleeding. The goal of urgent warfarin reversal is to elevate or replace vitamin K-dependent clotting factors. In the United States, fresh frozen plasma (FFP) is considered the standard of care for warfarin reversal. Prothrombin complex concentrates (PCCs) offer an alternative to FFP for rapidly replacing deficient clotting factors and correcting the international normalized ratio (INR). However, few prospective clinical trials have been conducted to evaluate the effectiveness of these concentrates relative to other treatment modalities. A review of the published literature over the last 30 years found that PCCs offer a rapid and specific method for replacing vitamin K-dependent clotting factors and restoring normal hemostasis in the context of over-coagulation. In those studies in which PCCs were compared with FFP, PCCs were found more effective in shortening the time to INR correction and were associated with a low risk of thrombotic adverse events. Evidence-based treatment guidelines are needed to optimize the use of PCCs for warfarin reversal.