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Invasive mechanical ventilation can successfully support the patient with acute respiratory failure, but it is associated with considerable risks. Numerous complications of invasive mechanical ventilation have been identified, and these may contribute to increased mortality. Therefore after clinical improvement has occurred, considerable emphasis is placed on expeditiously freeing the patient from the ventilator. This process of getting a patient off mechanical ventilation has been variably termed weaning, liberation, or discontinuation (terms which may be used interchangeably), and can be further divided into “readiness testing” and “progressive withdrawal.” Over the last decade, new developments in our understanding of the process of weaning have provided investigators with the tools to address a number of key questions: How should readiness for weaning (and trials of spontaneous breathing) be determined? What is the role of weaning parameters in deciding when to initiate the weaning process? What is the best mode for conducting a spontaneous breathing trial and how should the patient be monitored? What are the mechanisms for weaning (and spontaneous breathing trial) failure? What is the best technique to facilitate progressive withdrawal? What other factors can facilitate liberation from mechanical ventilation? What are the risks of extubation failure and how can extubation outcome best be predicted? What is the role for protocols in facilitating weaning from mechanical ventilation?