Prone positioning has been used to improve gas exchange in mechanically ventilated patients with severe acute respiratory failure. Brain injured patients have been excluded from this therapy due to its potential effects on intracranial pressure. Nonetheless, these patients are extremely sensible to hypoxemia, and their prognosis worsens dramatically when acute respiratory failure appears. We present three cases of brain injured patients (two with traumatic brain injury and one with intracerebral hemorrhage) with severe acute respiratory failure who were managed with prone positioning. Neurologic and respiratory outcomes were not unfavorable. We provide a brief review of the literature related to this matter.