Development of atelectasis is common in both patients with and without lung injury during mechanical ventilation. Atelectasis might contribute to or attenuate lung injury by different possible mechanisms. Possible direct effects of atelectasis include inflammatory activation or infection of the affected regional lung tissues. In addition, the loss of aerated lung volume due to atelectasis in mechanically ventilated patients indirectly results in increased mechanical strain of the reduced number of ventilated lung regions, if ventilation is not adequately decreased. This study discusses possible mechanisms and interactions between atelectasis formation in the lungs and the development or aggravation of acute lung injury.