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To describe the physiological meaning and the clinical application of the lung stress and strain concepts.The end-inspiratory plateau pressure and ratio of tidal volume/ideal body weight are inadequate surrogates for the end-inspiratory stress (equal to the transpulmonary pressure) and the end-inspiratory strain (change in lung volume relative to the resting volume). For a given plateau pressure or tidal volume/ideal body weight, stress and strain may vary largely due to the variability of chest wall elastance and the resting lung volume. The injurious limits of stress and strain in healthy lungs are reached when stress and strain reach the total lung capacity. This occurs when the resting lung volume (the baby lung in case of acute respiratory distress syndrome) is increased by two-fold to three-fold. As these limits are rarely reached in clinical practice and damage has been reported with stress and strain well below this upper limit, this implies the presence in the lung parenchyma of regions which act as stress raisers or pressure multipliers. These are primarily linked to the inhomogeneous distribution of local stress and strain.End-inspiratory stress and strain, as well as the lung inhomogeneity and the stress raisers, must be taken in account when setting mechanical ventilation.