Evidence has slowly accumulated over the years that mechanical ventilation can inflict damage to the lungs. This process, termed "ventilator-induced lung injury" (VILI), is the result of a complex interplay between various mechanical forces acting on alveoli during mechanical ventilation, in which volume, rather than pressure, seems to be the main culprit. Data from animal models strongly suggest that the two main determinants of VILI are alveolar overdistention and the repeated collapse and reopening of alveoli during the ventilatory cycle. Studies exploring the pathophysiologic mechanisms underlying VILI suggest that these mechanical forces probably exert their damaging effects through initiation of a localized inflammatory response, the latter being responsible for ongoing lung injury. If this is indeed the case, then strategies aimed at preventing VILI should be directed not only at reducing mechanical forces involved but also at modulating the inflammatory response elicited by these forces.