Objective: To critically evaluate the use of analgosedation in the management of agitation in critically ill mechanically ventilated patients. Data Sources: Literature was accessed through MEDLINE (1948-November 2011) and Cochrane Library (2011, issue 1) using the terms analgosedation, analgosedation, or analgesia-based sedation alone or in combination with intensive care unit or critically ill. Reference lists of related publications were also reviewed. Study Selection and Data Extraction: All articles published in English were evaluated. Randomized controlled trials examining critically ill mechanically ventilated patients older than 18 years were included. Data Synthesis: Limitations of current sedation practices include serious adverse drug events, prolonged mechanical ventilation time, and intensive care unit (ICU) length of stay. Studies have demonstrated that analgosedation, a strategy that manages patient pain and discomfort first, before providing sedative therapy, results in improved patient outcomes compared to standard sedative-hypnotic regimens. Nine randomized controlled trials comparing remifentanil-based analgosedation to other commonly used agents (fentanyl, midazolam, morphine, and propofol) for ICU sedation and 1 trial comparing morphine to daily sedation interruption with propofol or midazolam were reviewed. Remifentanil is an ideal agent for analgosedation due to its easy titratability and organ-in dependent metabolism. When compared to sedative-hypnotic regimens, remifentanil-based regimens were associated with shorter duration of mechanical ventilation, more rapid weaning from the ventilator, and shorter ICU length of stay. Compared to fentanyl-based regimens, remifentanil had similar efficacy with the exception of increased pain requirements upon remifentanil discontinuation. Analgosedation was well tolerated, with no significant differences in hemodynamic stability compared to sedative-hypnotic regimens. Conclusions: Analgosedation is an efficacious and well-tolerated approach to management of ICU sedation with improved patient outcomes compared to sedative-hypnotic approaches. Additional well-designed trials are warranted to clarify the role of analgosedation in the management of ICU sedation, including trials with nonopioid analgesics.