Ventilator-induced lung injury (VILI) has no definitive diagnostic criteria and its mechanisms are incompletely understood. They include barotrauma, volutrauma, ateletrauma, and biotrauma, caused by excessive distension of lung tissue, cyclic opening and closing of alveoli, and release of inflammatory mediators. New concepts such as patient self-inflicted lung injury (P-SILI) emphasize the role of respiratory drive and mechanical energy transfer. Prevention requires a dynamic strategy during mechanical ventilation. In the phase of controlled ventilation, lung protective ventilation with low tidal volume, driving pressure, individualized positive end-expiratory pressure, prone positioning and extracorporeal support is used. In the transition phase, breathing is modulated for patient-ventilator synchronization against P-SILI. In the weaning phase, spontaneous breathing tests are evaluated for the safe termination of ventilation.