Weaning from invasive mechanical ventilation is a critical phase of intensive care management. While structured protocols, daily readiness assessments, and spontaneous breathing trials (SBTs) improve outcomes in general ICU populations, their application in patients with acute brain injury (ABI) is challenging. In these patients, respiratory mechanics are frequently preserved, whereas impaired consciousness, ineffective airway protective reflexes, and excessive secretions predominantly determine extubation readiness and success. This narrative review reframes Boles’s Six Stages of Weaning within a neurocritical care perspective, incorporating ABI-specific considerations, including stabilization and pre-weaning optimization; suspicion that weaning may be possible; readiness assessment; performance of SBTs; extubation decision-making; and recognition and management of extubation failure. Across these stages, evidence consistently demonstrates that neurological factors, especially cough strength, swallowing function, ability to follow commands, and level of consciousness, are the main determinants of extubation success in ABI patients. In contrast, traditional respiratory predictors, such as rapid shallow breathing index (RSBI) or maximal inspiratory pressure (MIP)/negative inspiratory force (NIF), show limited discriminatory value in this population. Emerging data suggest that integrated models combining neurological and respiratory variables provide a more accurate framework for extubation decision-making in ABI. By highlighting the limitations of conventional weaning and extubation criteria, this review proposes practical, physiology-driven strategies to guide ventilator liberation in neurocritical care, with the goal of reducing extubation failure and minimizing secondary neurological injury.