Advances in separation techniques and biotechnology have contributed to the development of anticoagulant agents from hematophagous animals. The most potent known natural thrombin inhibitor from blood-sucking leeches (Hirudo medicinalis), hirudin has served as a standard for designing the natural coagulation inhibitors as an anticoagulant drug. The search for the development of hirudin from leech extract to genetically engineered products as an alternative anticoagulant has been resumed. The pharmacological profiling of the isolated thrombin inhibitor has shown that native hirudin is an antithrombotic agent of high quality. However, its clinical use has remained limited, because the substance has not been available in adequate amounts. The progress in molecular biology has stimulated the interest in the structure and function of hirudin. This development resulted in the production of recombinant hirudins (r-hirudins) through gene technology. The biological properties of hirudin combined with the ready availability of recombinant forms make the specific thrombin inhibitor well-suited for use as an antithrombotic drug. Its use should lead to a decisive progress in the management of thromboembolic diseases of both arterial and venous origin. Clinical trials, especially in diseases in which thrombin plays a crucial role, are in progress.