Heparin-induced thrombocytopenia (HIT) is a serious, prothrombotic, immune-mediated complication of heparin therapy that can cause limb- and life-threatening thromboembolic events. Prompt diagnosis and therapeutic dose anticoagulation by an alternative anticoagulant are crucial to improve clinical outcome. In critically ill patients, the diagnosis of HIT is difficult due to the high incidence of thrombocytopenia, often caused by reasons other than HIT, and the high incidence of clinically irrelevant, non-platelet-activating anti-PF4-heparin antibodies. Also, treatment of HIT is problematic in these patients. No antidote is available for any of the alternative anticoagulants, and their half-lives are often prolonged in the presence of renal or hepatic insufficiency. This increases the risk of bleeding complications and mandates careful balancing of both risks, thrombosis and bleeding. Therefore, accurate diagnosis of HIT and individual choice of alternative anticoagulant are important for the adequate management of critically ill HIT patients.