The primary purpose of mechanical ventilation is to decrease work of breathing. Achieving this goal requires that cycling of the ventilator be carefully aligned with the intrinsic rhythm of a patient's respiratory center output. Problems arise at the point of ventilator triggering, post-trigger inflation, and inspiration-expiration switchover. Careful, iterative adjustments of ventilator settings are required to minimize work of breathing. Use of protocols for the selection of ventilator settings can lead to complications (including alveolar overdistention) and risk of death. Because complications are axiomatic to mechanical ventilation, it should be discontinued at the earliest possible time. To shorten ventilator time, the critical step is to screen for weanability through use of weaning predictor tests. Use of T-tube trials circumvents the impossibility of estimating patient work of breathing during pressure support. Before extubation, patients should demonstrate the ability to breathe successfully in the absence of pressure support and positive end-expiratory pressure.