For the past five decades, vitamin K antagonists (VKA) have been the only class of oral anticoagulants available for treating or preventing venous and arterial thromboembolism. Recently, new oral anticoagulants were developed to address significant restrictions regarding the use of VKAs. These drugs act by direct blockade of activated coagulation factor X (FXa) or thrombin. This present mini-review highlights the pharmacological properties of these new anticoagulants, and discusses the supporting evidence for their usage as well as points to potential advantages and disadvantages of using these novel drugs in clinical practice.