In this issue of Anesthesiology Clinics, Guest Editors Pratik Panharipande and Wesley Ely look at modern sedation techniques in the critically ill. Topics include pharmacology of commonly used analgesics and sedatives in the ICU (including benzodiazepines, propofol, and opioids); pharmacology of sedative-analgesic agents (including dexmedetomidine, remifentanil, ketamine, volatile anesthetics, and the role of peripheral mu antagonists); lessons learned from international surveys of current sedation practices; protocolized and target-based sedation and analgesia in the ICU; sedation and weaning from mechanical ventilation, linking spontaneous awakening trials and spontaneous breathing trials to improve patient outcomes; altering ICU sedation paradigms to improve patient outcomes; sedation and sleep disturbances; sedation and immunomodulation; pharmacoeconomics of sedation; prevention and treatment of adult and pediatric delirium; and cognitive functioning, mental health and quality of life in ICU survivors.