In 2001, an International Consensus Conference stated that the use of NIV to “shorten weaning time and avoid reintubation represents a promising indication for NIV” but made no recommendation [4]. The authors of this statement also noted that, although NIV holds potential to improve physiologic outcomes without serious side effects in postoperative patients, the ability of NIV to “modify relevant clinical outcomes in these patients is less clear” [4]. In 2002, a British Thoracic Society guideline stated that “NIV has been used successfully to wean patients from invasive ventilation, and should be used when conventional weaning strategies fail.” The authors assigned a level B evidence grade to this recommendation and cited support from two randomized controlled trials (RCTs) [5]. Subsequently, the statement of the Sixth International Consensus Conference in Intensive Care Medicine on weaning from mechanical ventilation stated that “NIV techniques to shorten the duration of intubation should be considered in selected patients, especially those with hypercapnic respiratory failure and should not be routinely used as in the event of extubation failure” [6]. A more recent Canadian Clinical Practice Guideline [7] developed comprehensive recommendations for NIV use in weaning and extubation. First, it suggested that “NIV be used to facilitate early liberation from mechanical ventilation in patients who have COPD, but only in centers that have expertise.” This statement was designated as a Grading of Recommendations Assessment, Development and Evaluation (GRADE) 2B recommendation [8, 9]. Because of insufficient evidence, there was no recommendation regarding NIV for weaning in patients without COPD. Second, the guideline suggested “that NIV be used after planned extubation in patients who are considered to be at high risk of recurrent respiratory failure, but only in centers that have expertise in this type of therapy” (GRADE 2B recommendation) and suggested that NIV not be used after planned extubation in patients considered to be at low risk of respiratory failure (GRADE 2C recommendation). Finally, in the setting of post-extubation acute respiratory failure, it suggested that noninvasive positive pressure ventilation not be routinely used in patients who do not have COPD (GRADE 2C recommendation) and made no recommendation for patients with COPD because of a lack of evidence. In this chapter, we summarize current RCTs and meta-analyses pertaining to the application of NIV to wean patients from invasive ventilation, prevent extubation failure in at-risk patients, and to treat post-extubation respiratory failure.