Ventilator-induced lung injury (VILI) is a significant concern in mechanical ventilation, particularly in patients with acute respiratory distress syndrome (ARDS). Clinical and experimental studies have shown that high tidal volumes are harmful to the lungs. However, the exact mechanisms of lung injury and optimal ventilation strategies remain unclear. This chapter focuses on the mechanical and molecular mechanisms of VILI, the characteristics of bronchopulmonary dysplasia, and the potential for targeted therapy. The theory of a lung protective strategy involves preventing atelectasis and overinflation. However, applying these strategies in clinical practice is complex, especially in pediatric intensive care units, where most studies are based on adult patients. Experimental studies have shown that high tidal volumes and elevated airway pressures can cause VILI, but it is unclear which factor is most critical. Low tidal volumes are generally considered protective, but they can also lead to atelectasis, especially without positive end-expiratory pressure (PEEP). Studies have shown that low tidal volumes without PEEP can be harmful, particularly in the absence of pre-existing lung injury. The "baby lung" concept suggests that in extensively atelectatic lungs, low tidal volumes may overdistend the remaining aerated areas, causing injury. This is supported by observations of air cysts and bronchiectasis in non-dependent areas of ARDS patients. High PEEP is protective against injury with low tidal volumes, as demonstrated by the ALVEOLI study. This study showed that higher PEEP strategies were associated with better outcomes in ARDS patients. The mechanisms by which high PEEP protects the lungs are not fully understood, but they may involve improving oxygenation and reducing alveolar collapse. Overall, the optimal ventilation strategy for ARDS patients remains a topic of ongoing research and debate.Ventilator-induced lung injury (VILI) is a significant concern in mechanical ventilation, particularly in patients with acute respiratory distress syndrome (ARDS). Clinical and experimental studies have shown that high tidal volumes are harmful to the lungs. However, the exact mechanisms of lung injury and optimal ventilation strategies remain unclear. This chapter focuses on the mechanical and molecular mechanisms of VILI, the characteristics of bronchopulmonary dysplasia, and the potential for targeted therapy. The theory of a lung protective strategy involves preventing atelectasis and overinflation. However, applying these strategies in clinical practice is complex, especially in pediatric intensive care units, where most studies are based on adult patients. Experimental studies have shown that high tidal volumes and elevated airway pressures can cause VILI, but it is unclear which factor is most critical. Low tidal volumes are generally considered protective, but they can also lead to atelectasis, especially without positive end-expiratory pressure (PEEP). Studies have shown that low tidal volumes without PEEP can be harmful, particularly in the absence of pre-existing lung injury. The "baby lung" concept suggests that in extensively atelectatic lungs, low tidal volumes may overdistend the remaining aerated areas, causing injury. This is supported by observations of air cysts and bronchiectasis in non-dependent areas of ARDS patients. High PEEP is protective against injury with low tidal volumes, as demonstrated by the ALVEOLI study. This study showed that higher PEEP strategies were associated with better outcomes in ARDS patients. The mechanisms by which high PEEP protects the lungs are not fully understood, but they may involve improving oxygenation and reducing alveolar collapse. Overall, the optimal ventilation strategy for ARDS patients remains a topic of ongoing research and debate.