Oral anticoagulation therapy is transforming with the advent of the target specific oral anticoagulants, particularly, the direct thrombin inhibitors and factor Xa inhibitors. These agents have demonstrated clinical efficacy and safety and offer several potential advantages over current standard of care therapy, warfarin. Nevertheless, the pharmacology between the newly approved oral anticoagulants differs and must be considered for appropriate management and patient selection. The pharmacodynamics and pharmacokinetics of dabigatran etexilate, rivaroxaban, apixaban and edoxaban are discussed in detail, which may translate into considerable clinical implications.