Because of its rapid onset and offset of action, and its ability to be fully and rapidly reversed with protamine when anticoagulation control is needed, unfractionated heparin (UFH) remains the anticoagulant of choice in many intensive care unit (ICU) patients, particularly those with severe multi-organ failure or extracorporeal circuits, including extracorporeal membrane oxygenation (ECMO). UFH is a mixture of glycosaminoglycans purified from porcine intestine or bovine lung, which acts as a catalyst for antithrombin, an endogenous inhibitor of thrombin (factor IIa), factor Xa, and several other coagulation factors [1]. Binding of UFH to antithrombin is mediated by a unique pentasaccharide sequence that is present in only one-third of heparin chains [2]. A major drawback of UFH is the large inter-individual variability of its anticoagulant effect [2]. Heparin resistance could be defined as UFH failure to achieve a specified anticoagulation level despite the use of what is considered to be an adequate dose of heparin [3]. In our opinion, the arbitrary definition of the requirement of > 35,000 units of UFH per day to maintain an activated partial thromboplastin time (aPTT) within the target therapeutic range reported in patients with venous thromboembolism [3] is inappropriate in ICU patients since it does not take into account body-weight, clinical setting, and the occurrence of thrombotic complications. Furthermore, this definition has not been validated in clinical trials. A weight-based definition (IU/kg/hour) may be more appropriate, but consensus is still lacking.