The development of synthetic inhibitors of thrombin and of related arginine-specific esteroproteases is reviewed. The superiority of bis- and tris-benzamidines over benzamidine is discussed and related to the presence on the enzyme of secondary binding sites beyond the specificity pocket. It is demonstrated that inhibitors with marked specificity for a single enzyme can be produced, and with the help of such selective compounds it is shown that inhibition of factor Xa is more significant for overall anticoagulant effect than inhibition of thrombin.