Oral anticoagulation used to be synonymous with warfarin until the recent approval of oral direct thrombin inhibitors and factor Xa inhibitors in United States and other countries across the world. Thrombosis prevention and treatment continue to be the main objective and goal for surgical and medical patients. Regulatory agencies continue to revise their guidelines to treat these patients with appropriate medication and for optimal duration. As the choices for oral anticoagulants increase, with many oral anticoagulant drugs currently in the pipeline awaiting completion of clinical trials, the guidelines for venous thromboembolism prevention, stroke prevention in atrial fibrillation, and treatment of acute arterial and venous thrombi will also shift from the current standards to new standards set by these clinical trials for optimal dosing and duration of treatment. However, it must be reinforced that these new oral anticoagulants are distinct pharmacological compounds with specific targets and will also have distinct clinical indications for use.