Acute Respiratory Distress Syndrome (ARDS) accounts for 10% of ICU admissions and affects 3 million patients each year. Despite decades of research, it is still associated with one of the highest mortality rates in the critically ill. Advances in supportive care, innovations in technologies and insights from recent clinical trials have contributed to improved outcomes and a renewed interest in the scope and use of Extracorporeal life support (ECLS) as a treatment for severe ARDS, including high flow veno-venous Extracorporeal Membrane Oxygenation (VV-ECMO) and low flow Extracorporeal Carbon Dioxide Removal (ECCO2R). The rationale being that extracorporeal gas exchange allows the use of lung protective ventilator settings, thereby minimizing ventilator-induced lung injury (VILI). Ventilation strategies are adapted to the patient’s condition during the different stages of ECMO support. Several areas in the management of mechanical ventilation in patients on ECMO, such as the best ventilator mode, extubation-decannulation sequence and tracheostomy timing, are tailored to the patients’ recovery. Reduction in sedation allowing mobilization, nutrition and early rehabilitation are subsequent therapeutic goals after lung rest has been achieved.