Thromboembolic events commonly occur in critically ill patients, and although they do not consistently present with specific signs and symptoms, they are associated with high morbity and mortality. Antithrombotic agents are the mainstay of the prevention and treatment of venous thromboembolism, and they are also used for stroke prevention in atrial fibrillation, embolism prevention in heart failure, and anticoagulation of prosthetic valves. These drugs have been combined with antiplatelet therapy for the prevention of secondary acute coronary syndrome. Antithrombotic agents such as Aspirin, clopidogrel, vitamin K antagonists and fondaparinux, an indirect Factor Xa inhibitor, are already incorporated into our clinical practice. New small-molecule, selective Factor Xa and thrombin inhibitors that simultaneously inhibit free plasma and clot-associated factor activities have received considerable attention recently. These new oral anticoagulants are in various phases of clinical development. dabigatran, rivaroxaban and apixaban are in more advanced phases of clinical development and are already available in a number of countries. This review article highlights the studies describing the use of these three anticoagulants in an intensive care setting.