Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening adverse drug reaction that may develop in certain patients exposed to heparin and is caused by antibodies with specificity for chemokine CXCL4 (formerly known as platelet factor 4)/heparin complexes. Rapid diagnosis and intervention is key to prevent severe thrombotic complications. The immunobiology of HIT is atypical as the immune reaction most often involves rapid generation of immunoglobulin class G within 5-14 days after heparin exposure, and apparently lacks memory as patients may be reexposed to heparin. This report reviews clinical presentation, diagnostic issues, and immunobiology of HIT.