Sedation and analgesia are essential practices in the intensive care unit (ICU), providing comfort, pain relief, and anxiety reduction for critically ill patients. The appropriate administration of sedatives and analgesics is critical to improving clinical outcomes, minimizing complications, and reducing costs associated with ICU care. It is commonly used in patients undergoing mechanical ventilation (MV), where it helps achieve patient-ventilator synchrony and improves tolerance to the ventilator. However, withdrawal of sedation is an essential step in initiating the weaning process from MV, allowing assessment of the patient’s readiness for extubation and reducing the risks associated with prolonged ventilation. Daily awakening strategies, the rational use of sedatives and analgesics, and the adoption of nurse-controlled sedation protocols are essential measures to optimize patient outcomes, reduce complications, and shorten the length of stay. This chapter reviews the principles, pharmacologic agents, and management strategies for sedoanalgesia during weaning of ICU patients from mechanical ventilation.