The existence of ventilation/ventilator-induced lung injury (VILI) during spontaneous breathing cannot be denied, as it has been shown experimentally [1] and, at least, suspected in some clinical circumstances [2]. Therefore it is nonsense to be pro or con towards the facts. One, however, may be pro or con the opinion that spontaneous breathing, either with or without mechanical ventilation, favors a lower occurrence of ventilator-induced lung injury (VILI) compared to mechanical ventilation alone. Before discussing this problem, it is convenient to precisely define the VILI and the conditions for its development.We define here VILI as the mechanical lesions which develop in the lung when an "excessive" mechanical power is transferred to the lung parenchyma [3]. We will not therefore consider here other situations such as pneumonia or deterioration of hemodynamic-related lung edema, which may be associated with mechanical ventilation or spontaneous breathing, but are not necessarily linked to the mechanical forces. The mechanical lesions develop in the interstitial space as microfractures of the matrix [4] or of the capillary walls [5,6]. In fact, when the polymers composing the extracellular matrix are overstretched, some of the molecular bonds will break, generating polymers of lower molecular weight, which in turn, via toll receptors, may activate the inflammatory cascade [7]. The microfractures may be considered analogous to those of metals undergoing repeated cycles of high stress and strain. They require several cycles (i.e., time) to develop, but when they occur the lesions spread rapidly throughout the material [8].For VILI to occur, however, two conditions are required. The first is ventilator-related and is the mechanical power. This is composed of the product of tidal volume, driving pressure, and respiratory rate, to which the contribution of the positive end-expiratory pressure must be added [9]. The second condition for VILI development is lung-related and is primarily the extent of the inflammatory edema. The greater it is, the lower the ventilatable lung size is and the greater the lung parenchyma inhomogeneity becomes. The mechanical power, the lung size, and the extent of inhomogeneity obviously interact in the generation of VILI.In this context, we may discuss the main differences (and the consequences on VILI) between spontaneous and mechanical ventilation.The main differences are related to:1. Intrathoracic pressure It is negative and/or decreases during the inspiration in spontaneous breathing, while it is positive and/or increases during the inspiration in mechanical ventilation. 2. Diaphragm dynamics During spontaneous efforts the posterior portion of the diaphragm moves caudally to a greater extent than the anterior-ventral portion, whereas this does not occur during passive inflation. 3. Power source The energy is provided by the respiratory muscles during spontaneous breathing and by electrical power during mechanical ventilation (note that the greater the contribution of the respirato...