Members of the serine protease inhibitor (serpin) superfamily play import-ant roles in the inhibition of serine proteases involved in complex systems. This is evident in the regulation of coagulation serine proteases, especially the central enzyme in this system, thrombin. This review focuses on three serpins which are known to be key players in the regulation of thrombin: antithrombin and heparin cofactor II, which inhibit thrombin in its pro-coagulant role, and protein C inhibitor, which primarily inhibits the throm-bin⁄thrombomodulin complex, where thrombin plays an anticoagulant role. .