Mechanical ventilation (MV) is a primary support for respiratory failure patients. However, patient condition and response to treatment are heterogeneous and variable over time. Thus, general, one size fits all treatment approaches may not be suitable, and a more individualized approach could improve care and outcomes. Model-based therapy offers the opportunity to individualise MV to patient-specific needs at any given interval. It uses real-time identified patient-specific respiratory system model parameters to personalise and optimize care. This talk focuses on the journey from conceptual model-based MV ideas, through clinical proof of concept, and finally to a large randomized controlled trial.