The process of withdrawing mechanical ventilation is commonly referred to as 'weaning', but in the literature the term has acquired two distinct meanings, having been described as either (1) the process of gradually decreasing ventilatory support to return the work of breathing back to the patient or (2) a means of determining when patients have the ability to be safely liberated from the ventilator. In this chapter the term 'weaning' refers to the process of returning the work of breathing back to the patient. Determining readiness for extubation or de-cannulation is dealt with as a separate issue. Un-assisted spontaneous ventilation has two indispensable requisites: firstly, the ability to initiate rhythmic inspiratory effort, and secondly the muscular strength and stamina to maintain tidal ventilation. The establishment of a spontaneous respiratory rhythm is challenged in three ways: primary post-ventilation apnoea, failure to sustain an acceptable minute ventilation, and repeated periods of apnoea.