Heparin resistance (HR) on ECMO exacerbates bleeding and thrombogenesis. So far, there is no universal definition of HR on ECMO and no unified strategy for the assessment of heparin efficacy in ECMO patients. The most frequent discrepancy in defining HR is the difference in reported doses: units per day (U/d) or per kilogram per hour (U/kg/h). Another disagreement occurs ow-ing to different ways of measuring UFH efficacy, contributing to further disagreement in a com-mon definition of HR. Due to numerous processes that start with ECMO initiation, including protein layer formation on the surface of the circuits, recruitment of immune cells, activation of complement and contact activation systems, and platelets, the assessment of pure antithrombin consumption is complicated. Moreover, there is an alternative anticoagulation performed by a serine protease inhibitor named Heparin Cofactor II, the contribution of which could also be measured on heparin consumption. Considering simultaneously launched processes of inflam-mation and thrombogenesis in response to contact with artificial surfaces on ECMO, we listed possible mechanisms contributing to additional antithrombin consumption. The effect of the flow on the platelets activation and vWF assembly was also described. We examined the literature from Pubmed and Embase to find possible definitions of heparin resistance on ECMO among pediatric and adult cohorts. We extracted 13 records with different HR assessment approaches and sug-gested our vision of delineating HR on ECMO.