Veno-venous extracorporeal membrane oxygenation (V-V ECMO) is a complex and invasive intervention used increasingly in the management of severe respiratory failure. Once established, the management of prolonged V-V ECMO support involves balancing priorities of lung protection, prevention of pulmonary complications, sedation weaning and safe reduction in ECMO support. These occur variably as the pulmonary pathology resolves and ECMO support is reduced. Evidence based strategies to assist clinicians during prolonged V-V ECMO support are lacking, with the majority of literature focussing on ventilation strategies following ECMO initiation and the criteria for separation from V-V ECMO once liberation is considered safe. Practice is largely clinician and institution dependent with significant heterogeneity. There are numerous questions which remain unanswered regarding the prioritisation and strategies for safe V-V ECMO weaning. This review aimed to provide a novel conceptual framework to assist clinicians by dividing prolonged V-V ECMO support into six phases: ultra-lung-protective, lung protective, transition to spontaneous breathing, liberation trial, decannulation and post decannulation support. We reviewed existing literature and identified knowledge gaps for future research.