The development of new antithrombotic agents has been stimulated by clinical needs and by advances in biotechnology that have made it possible to produce drugs that target specific steps in thrombogenesis. Heparin has pharmacokinetic and biophysical limitations that are overcome by new anticoagulants. Of these, low-molecular-weight heparin and direct inhibitors of thrombin have been evaluated clinically. Coumarins require careful laboratory monitoring because of concerns about safety. Orally active direct inhibitors of thrombin and factor Xa may replace coumarins. Aspirin is of limited efficacy because it inhibits only one pathway of platelet activation. Inhibitors of adenosine diphosphate receptor and glycoprotein IIb/IIIa antagonists are more effective than aspirin and are used in the clinic.