Heparin‐induced thrombocytopenia (HIT) is a relatively common prothrombotic adverse effect of heparin both unfractionated and (less often) low‐molecular‐weight heparin caused by antibodies that recognize multimolecular complexes of (positively charged) platelet factor 4 (PF4) bound to (negatively charged) heparin. The antibodies strongly activate platelets through their Fc?RIIa receptors, producing a procoagulant platelet response that results in hypercoagulability and increased thrombotic risk. Certain tests for HIT antibodies, such as PF4‐dependent immunoassays and platelet activation assays, are very sensitive; thus, a negative test result essentially rules out HIT (high negative predictive value). However, only approximately half of immunoassay‐positive patients (and only 15% among critically ill patients) also have a positive platelet activation assay, and thus the possibility of ‘true’ HIT. Treatment of acute HIT emphasizes substitution of heparin with a nonheparin anticoagulant, such as indirect, antithrombin‐dependent factor Xa inhibitors (e.g. danaparoid, fondaparinux) or direct thrombin inhibitors (e.g. argatroban, recombinant hirudin, bivalirudin), while vitamin K antagonists must be avoided.