Heparin has been the mainstay of treatment and prevention of venous and arterial thromboembolism for many years. Its use, however, is associated with a serious and potentially fatal immunological drug reaction termed heparin-induced thrombocytopenia (HIT). Current treatment consists of discontinuing heparin therapy and the administration of an alternate anticoagulant (e.g. danaparoid, lepirudin, bivalirudin or argatroban). Fondaparinux is a novel synthetic heparin pentasaccharide capable of inhibiting factor Xa via the action of antithrombin (AT) but devoid of anti-factor IIa (thrombin) activity. Although the drug is identical in structure to the pentasaccharide domain found on unfractionated heparin (UH), it is too small to be recognized by the majority of heparin-reactive antibodies. It is theoretically an excellent candidate agent for the treatment of HIT. Currently, fondaparinux is licensed for orthopaedic venous thromboprophylaxis but not for the treatment of HIT. Successes in the use of fondaparinux in the treatment of HIT, as demonstrated in recent published case reports, warrant further study in larger controlled trials for this indication.