Treatment with heparin is associated with two types of thrombocytopenia. One is a mild, transient, nonimmune disorder, generally without adverse clinical consequence. The other, known as heparin-induced thrombocytopenia (HIT), is a potentially serious, immunoglobulin-mediated reaction with a paradoxic high risk of thromboembolic events. Various treatment options for HIT are discussed, with emphasis on pharmacologic approaches that control the increased thrombin generation characteristic of this disorder.