BACKGROUND: Lepirudin is a recombinant hirudin that exerts its anticoagulant effect by direct inhibition of thrombin. Lepirudin is indicated for anticoagulation in patients with heparin-induced thrombocytopenia (HIT) and associated thromboembolic disease to prevent further thromboembolic complications. OBJECTIVE: This review addresses various clinical uses of lepirudin including but not limited to FDA approved indication. The objective is to provide an updated overview of the clinical use and pharmacology of the agent. In addition, we address certain areas of controversy especially pertaining to dosing of lepirudin and its use in different clinical situations. METHODS: Literature was reviewed using appropriate search terms in Pubmed and Ovid medline databases. RESULTS/CONCLUSION: Lepirudin continues to be a valuable anticoagulant in the management of HIT. Lepirudin has the highest recommendation in treatment of HIT based on evidence from clinical trials. Minor modifications in dosing over the standard label recommendations may simplify its use and enhance safety.