Venous thromboembolism (VTE) is a major public health issue, with a high incidence in hospitalised patients. Furthermore, many VTE events are preventable with appropriate thromboprophylaxis. Medical thromboprophylaxis usually comprises heparins, while warfarin has been the mainstay of long term anticoagulation for many years. Both drugs are limited by their narrow therapeutic index and the need for regular monitoring. The introduction of low molecular weight heparins and fondaparinux has overcome some of these shortfalls but their use remains restricted by requisite parenteral administration. There is a clear need for new anticoagulants with predictable pharmacokinetics and anticoagulant effect. To this end, 2 new agents; dabigatran and rivaroxaban, have recently been licensed for use in orthopaedic thromboprophylaxis. This review discusses the limitations of traditional anticoagulants, and summarises the development and clinical studies pertaining to the use of 3 new targeted anticoagulants: idraparinux, rivaroxaban and dabigatran in VTE, in addition to the limitations of these novel agents.