Traditional therapeutic oral anticoagulation strategies often require invasive dosing or monitoring. Vitamin K antagonists (VKAs) have a large number of interactions, delayed onset requires frequent dose monitoring, and they have a small margin between therapeutic dose and bleeding complications. Novel oral anticoagulants, such as dabigatran, rivaroxaban and apixaban, are being developed to prevent those VKAs drawbacks. Besides oral bioavailability, those compounds are designed to require minimal to no monitoring and have a favourable safety profile. This review reports efficacy and safety data of these compounds throughout clinical development, as well as new approaches for oral pharmacological management of venous thromboembolism.