Venous thromboembolic diseases are among the most important causes of morbidity and mortality in Canada. Agents which interfere with the coagulation mechanism are highly effective in treating these disorders, but at the potentially high cost of serious hemorrhagic complications. The optimal prevention of both serious outcomes and complications of therapy can be achieved by prophylactic treatment of high risk patients. Heparin and vitamin K antagonists remain the mainstays of antithrombotic therapy. The pharmacology of these agents is reviewed, and a rational approach to their clinical use is presented.