Hirudin is the most potent natural inhibitor of thrombin known to date. It is gaining popularity as an anticoagulant now that recombinant and synthesized forms are available. It is a monospecific and co-factor-independent thrombin inhibitor with otherwise inert pharmacological properties. Being a surprisingly weak immunogen, its administration has exhibited no side effects, particularly on platelets. Bleeding complications are not to be expected at therapeutic doses. Effective anticoagulatory doses can be easily predicted and laboratory control is no problem. Application of hirudin or derivatives thereof may be indicated for: prophylaxis and treatment of postoperative venous thrombosis and diffuse microthrombosis; prevention of arterial thrombosis, especially in cardiac surgery; enhancement of fibrinolytic therapy and/or angioplasty to prevent reocclusion; extracorporeal circulation; and plastic surgery. Hirudin may be a particularly useful alternative anticoagulatory agent in patients sensitized to heparin or in patients with hereditary or acquired antithrombin III deficiency. However, whether hirudin is really an effective therapeutic tool and whether it can replace heparin in certain clinical indications can be judged only after extended clinical experience has been accumulated.