Critically ill patients are frequently prescribed sedatives and analgesics to ensure patient safety, to relieve pain and anxiety, to reduce stress and oxygen consumption, and to prevent patient ventilator dysynchrony. Recent studies have revealed that these medications themselves contribute to worsening clinical outcomes. An evidence-based organizational approach referred to as the ABCDE bundle (Awakening and Breathing Coordination of daily sedation and ventilator removal trials; Choice of sedative or analgesic exposure; Delirium monitoring and management; and Early mobility and Exercise) is presented in this commentary.