While being an essential part of general anesthesia for surgery and at times even a life-saving intervention in critically ill patients, mechanical ventilation has a strong potential to cause harm. Certain ventilation strategies could prevent, at least to some extent, the injury caused by this intervention. One essential element of so-called 'lung-protective' ventilation is the use of lower tidal volumes. It is uncertain whether higher levels of positive end-expiratory pressures have lung-protective properties as well. There are indications that too high oxygen fractions of inspired air, or too high blood oxygen targets, are harmful. Circumstantial evidence further suggests that spontaneous modes of ventilation are to be preferred over controlled ventilation to prevent harm to respiratory muscle. Finally, the use of restrictive sedation strategies in critically ill patients indirectly prevents ventilation-induced injury, as daily spontaneous awakening and breathing trials and bolus instead of continuous sedation are associated with shorter duration of ventilation and shorten the exposure to the injurious effects of ventilation.