The determination of optimal timing of liberation from mechanical ventilation requires a thorough assessment of multiple variables that can result in extubation failure. It is estimated that 5-20% of extubations fail. Traditional weaning parameters fail to predict extubation failure accurately, and attention has thus turned to improvements in extubation decision making through assessment of elements that may result in inability to protect the airway, such as excessive respiratory secretions, inadequate cough, and depressed mental status. Extubation is particularly controversial in patients with depressed mental status and inability to follow commands. When looking at univariate analyses, the reported studies are relatively evenly divided among those that did and did not find that inability to follow commands (ie, abnormal mental status) increases the risk of extubation failure. In addition, although extubation failure is a risk factor for poor overall outcome in heterogeneous populations, its impact on the patient failing with neurologic dysfunction has not been adequately determined. One limiting factor in all reported studies is how "inability to follow commands" is defined. The majority of studies use the Glasgow coma score, but this is difficult to determine in the intubated patient. Moreover, using the cutoff of Glasgow coma score >or= 8, favored by many authors, is questionable, as some patients with higher scores may be unable to follow commands. Currently it is agreed that many patients who are unable to follow commands, but have the ability to clear pulmonary secretions, can be safely extubated. A prospective, randomized trial using a more specific definition of "following commands" would certainly help remove some of the uncertainty in this patient population.