Heparin-induced thrombocytopenia (HIT) is classified as two distinct entities: HIT I and HIT II. HIT I is mild thrombocytopenia that occurs in approximately 25% of patients within the first 5 days of starting therapy and is clinically benign. HIT II is a syndrome of severe thrombocytopenia and thrombosis that occurs 6 days to 14 days into therapy in about 2% of patients and is associated with considerable morbidity and mortality. The severe form of HIT appears to be due to antibodies directed against a complex of heparin and platelet factor 4 (PF4) that leads to platelet activation, endothelial injury, and thrombosis. Treatment is problematic, but heparin administration must be immediately discontinued. In uncontrolled trials, agents such as warfarin, hirudin, and danaparoid have shown some efficacy. Early recognition by monitoring daily platelet counts during therapy may decrease the incidence of thrombosis.