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Delirium and ICU-acquired weakness are frequent in critically ill mechanically ventilated patients. The number of mechanically ventilated patients is increasing, placing more patients at risk for these adverse outcomes. Sedation is given to ensure comfort and to minimize distress, but is linked to delirium and immobility. We review recent findings on the management of mechanically ventilated patients focusing on strategies that may improve neurologic and functional outcomes in critically ill patients.We present the evidence-based ‘ABCDE’ bundle, an integrated and interdisciplinary approach to the management of mechanically ventilated patients. Spontaneous awakening and breathing trials have been combined into ‘awake and breathing coordination’, shortening the duration of mechanical ventilation, ICU and hospital length of stay and improving survival. The choice of α-2 agonists reduces ICU delirium and duration of mechanical ventilation. Delirium monitoring improves recognition of this disorder, but data on pharmacologic treatment are mixed. Early mobility and exercise may reduce physical dysfunction and delirium rates.Outcomes of critically ill patients can be improved by applying evidence-based therapies for the ‘liberation’ from mechanical ventilation and sedation, and the ‘animation’ through early mobilization. Clinicians should be aware of organizational approaches such as the ‘ABCDE’ bundle to improve the management of mechanically ventilated patients.