In the intensive care unit (ICU), weaning from mechanical ventilation follows a step-by-step process that has been well established in the general ICU population. However, little data is available in brain injury patients, who are often intubated to protect airways and prevent central hypoventilation. In this narrative review, we describe the general principles of weaning and how these principles can be adapted to brain injury patients. We focus on three major issues regarding weaning from mechanic ventilation in brain injury patients: (1) sedation protocol, (2) weaning and extubation protocol and criteria, (3) criteria, timing and technique for tracheostomy.