Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication that can occur after exposure to heparin products. Because patients with HIT are at increased risk for thrombosis, anticoagulation is warranted. The direct thrombin inhibitors lepirudin and argatroban are approved by the United States Food and Drug Administration (FDA) for this indication. Bivalirudin, another direct thrombin inhibitor, is approved for use in patients with HIT who must undergo percutaneous coronary intervention. The synthetic pentasaccharide fondaparinux lacks FDA approval for treating patients with HIT; however, a few published reports describe its use. Furthermore, various small-scale, in vitro studies have demonstrated a lack of cross-reactivity between fondaparinux and HIT antibodies. Large, in vivo comparison trials must be performed before fondaparinux can become a standard treatment option in the setting of HIT.