Patients undergoing surgery receive anticoagulation for perioperative thromboprophylaxis or ischemic cardiovascular disease. Because anticoagulants may also potentiate bleeding, clinicians need to understand the implications of anticoagulation in perioperative and postoperative patient management. Many newer anticoagulants that are now available or are in clinical development do not require routine coagulation monitoring, have more predictable dose responses, and have fewer interactions with other drugs and food. The most advanced oral anticoagulants in clinical development are the direct factor Xa inhibitors rivaroxaban and apixaban, and the direct thrombin inhibitor dabigatran etexilate. These agents have been evaluated in the postoperative setting in patients undergoing total hip- or knee-replacement surgery with promising results, and it remains to be seen whether these results will translate into other surgical settings. The impact of the new agents will be influenced by the balance between efficacy and safety, improved convenience, and potential cost-effectiveness benefits.