Sedation and analgesia constitute one of the cornerstones in the management of the critically ill patients. Most patients admitted to an Intensive Care Unit require prolonged sedation and analgesia. It has been demonstrated that adequate sedo- analgesia lessens stress-related events in the critically ill patients, facilitating their management and improving their outcomes. However, the use of sedatives and analgesics, especially when administered in continuous intravenous infusion, may have its complications derived from its infra or over utilization with proved impact on the outcome of critically ill patients. A proper monitoring and the implementation of sedation and analgesia protocols warrant the adequate management of existing sedatives aiding to avoid tolerance and dependency events. Strategies such as "sequential sedation", "dynamic sedation" or "daily sedation interruption" have been proposed as efficacious tools for the avoidance of complications related to prolonged sedation. In the present chapter, concepts related to prolonged sedation (meaning sedation for more than 72 hours) are reviewed; available agents are evaluated and strategies aimed to assure quality in its application are described.