Although life-saving, mechanical ventilation is associated with numerous complications. Recently, it was shown in animal models that controlled mechanical ventilation (CMV) can cause the so-called ventilator-induced diaphragmatic dysfunction (VIDD). The decrease in diaphragmatic strength proceeds along with prolonged mechanical ventilation. The decrease in diaphragmatic force occurs during CMV rather than during assisted modes of ventilation. Different mechanisms may cause VIDD: muscle atrophy, oxidative stress, structural injury and muscle fibre remodelling have been demonstrated in animal models. Although most critically ill patients receiving mechanical ventilation show profound diaphragmatic weakness, clear evidence supporting the existence of VIDD is still lacking. Since VIDD is particularly caused by comorbidity, a series of other factors may lead to diaphragmatic dysfunction. Whether or not VIDD causes weaning failure is difficult to decide since other reasons may also cause respiratory muscle weakness. However, based on pathophysiology, treatment options may be assisted mechanical ventilation, administration of antioxidative agents or stimulation of the phrenic nerve.