Venovenous extracorporeal membrane oxygenation (VV ECMO) is a potentially lifesaving yet resource-intensive organ support option for patients with very severe respiratory failure refractory to optimized conventional management. Mortality remains high, and ECMO is associated with significant complications, including bleeding, thrombosis, and vascular injury. Indication and timing of ECMO initiation are critical, as premature and also delayed use can affect outcomes. Current evidence, including findings from the CESAR and EOLIA trials and subsequent meta-analyses, supports the consideration of ECMO in very severe acute respiratory distress syndrome (ARDS) when lung-protective ventilation, prone positioning, and adjunctive therapies fail to ensure adequate gas exchange. Patient selection should rely on individualized risk-benefit assessment considering age, comorbidities, organ dysfunction, reversibility of lung injury, and patient-centered goals, rather than any single exclusion criterion. Management during ECMO focuses on ultra-protective ventilation to minimize ventilator-induced lung injury, early detection of complications, and tailored anticoagulation strategies, although optimal anticoagulation protocols remain undefined. When performed in experienced centres, prone positioning during ECMO is feasible and safe, but evidence for a survival benefit is inconclusive. Extracorporeal carbon dioxide removal (ECCO₂R) may facilitate ultra-protective ventilation but lacks a proven mortality benefit. Therefore, its use is currently not recommended outside the setting of well-designed clinical trials. Weaning from ECMO should be structured and guided by physiological readiness while maintaining lung-protective ventilation. Optimal outcomes are achieved in high-expertise, multidisciplinary centres, with ongoing research needed to refine patient selection, ventilation strategies, and complication management. Overall, VV ECMO remains an essential tool in the management of severe respiratory failure, requiring careful balancing of risks, resources, and individualized clinical decision-making.