Mechanical ventilation may lead to lung injury depending on the ventilatory settings (e.g. pressure amplitudes, endexpiratory pressures, frequency) and the length of mechanical ventilation. Particularly in the inhomogeneously injured lungs of ARDS patients, alveolar overextension results in volutrauma, cyclic opening and closure of alveolar units in atelectrauma. Particularly important appears to be the fact that these processes may also cause biotrauma, i.e. the ventilator-induced hyperactivation of inflammatory responses in the lung. These side effects are reduced, but not eliminated with the currently recommended ventilation strategy with a tidal volume of 6 ml/kg idealized body weight. It is our hope that in the future optimization of ventilator settings will be facilated by bedside monitoring of novel indices of respiratory mechanics such as the stress index or the Slice technique, and by innovative real-time imaging technologies such as electrical impedance tomography.