Heparin-induced thrombocytopenia (HIT) is an immune reaction in response to platelet factor 4-heparin complexes, which results in increased platelet activation and thrombocytopenia beginning on the 4th-5th day after heparin exposure induced by IgG antibody production. Platelet activation can lead to arterial thrombosis, but more commonly platelet microparticle formation contributes to venous thrombosis. Accurate diagnosis of HIT is based on the presence of clinical features, including a 50% fall in platelet count, appropriate timing of thrombocytopenia, development of new thrombosis despite thrombocytopenia and heparin therapy, and the absence of a more likely cause of thrombocytopenia. Documentation of an anti-PF4-heparin antibody is necessary, but is not sufficient to make the diagnosis since antibody formation occurs in a variety of clinical settings without the development of thrombocytopenia or thrombosis. Once HIT is suspected or confirmed, all forms of heparin should be discontinued and an alternative form of anticoagulation should be administered until the platelet count recovers. Treatment options include intravenous administration of argatroban, lepirudin, and bivalirudin; subcutaneous administration of fondaparinux has also been described. Warfarin therapy, if indicated, should be avoided until platelet recovery. Re-exposure to heparin can be avoided by use of alternative anticoagulants for most circumstances. Heparin-induced thrombocytopenia (HIT) has been the focus of increasing attention over the past 15-20 years. As interventions for HIT are developed, there is a need to accurately diagnose the condition, which can be challenging especially in severely ill patients.