Thrombosis, either venous and arterial, is the most important cause of death in our society. Thrombin formation is a pivotal step in the pathogenesis of both forms of thrombosis. Drugs like heparin and vitamin K antagonists act because they inhibit thrombin formation. Better drugs than conventional heparin and oral anticoagulants are however urgently needed. They can be found on basis of a better understanding of thrombin formation. The mechanism of thrombin formation is explained. The mode in which conventional heparin and the newer, low molecular weight heparins inhibit this process is discussed. It is shown that, contrary to current belief, low molecular weight heparins inhibit primarily via their action on thrombin and that the inhibition of factor Xa is of less importance. Thrombin inhibition has a direct action but also acts indirectly via its influence on thrombin mediated feedback loops. It is argued that rather than anti-factor Xa activity or prolongation of some type of coagulation time, the time-concentration integral of thrombin (thrombin potential) in clotting plasma should be used as a yardstick for the efficiency of a thrombin inhibiting drug.