Mechanical ventilation (MV) is the main supportive treatment in respiratory failure due to different etiologies. However, MV might aggravate ventilator-associated lung injury (VALI). Four main mechanisms leading to VALI are: 1) increased stress and strain, induced by high tidal volume (VT); 2) increased shear stress, i.e. opening and closing, of previously atelectatic alveolar units; 3) distribution of perfusion and 4) biotrauma. In severe acute respiratory distress syndrome patients, low VT, higher levels of positive end expiratory pressure, long duration prone position and neuromuscular blockade within the first 48 hours are associated to a better outcome. VALI can also occur by using high VT in previously non injured lungs. We believe that prevention is the target to minimize injurious effects of MV. This review aims to describe pathophysiology of VALI, the possible prevention and treatment as well as monitoring MV to minimize VALI.