In patients with the acute respiratory distress syndrome(ARDS), mechanical ventilation can cause ventilator-induced lung injury (VILI) through multiple mecha-nisms, including volutrauma, barotrauma, atelectrauma,myotrauma, and biotrauma [1]. In the most severe formsof ARDS, the smaller the baby lung, the greater thepotential for unsafe ventilation despite mechanical ven-tilation volume and pressure limitation. To further limitthe energy transmitted to the lungs by the mechanicalventilator, “ultra-lung-protective” ventilation reducingtidal volume (≤ 4 ml/kg), respiratory rate (< 20/min), andairway (plateau pressure < 25 cmH2O and driving pres-sure ≤ 15 cmH2O) pressures has been proposed [2]. How-ever, this strategy can result in severe respiratory acidosiswithout extracorporeal gas exchange using extracorpor-eal life support (ECLS) devices. Venovenous extracor-poreal membrane oxygenation (VV-ECMO) is a form ofECLS that provides full extracorporeal blood oxygenationand carbon dioxide removal, which can replace pulmo-nary function. VV-ECMO allows marked reductions intidal volume, respiratory rate, plateau and driving pres-sures [3, 4]. It has been associated with survival benefitsin randomized controlled trials (RCTs) and meta-analy-ses [3–6]. However, optimal mechanical ventilation set-tings on ECMO are still debated. In this narrative review,we summarize the current knowledge, rationale, and evi-dence for mechanical ventilation management and moni-toring in patients receiving VV-ECMO for severe ARDS.We will also discuss the research agenda in this field.