A minority of ICU patients have an indication for continuous deep sedation, for reasons such as the treatment of intracranial hypertension, severe respiratory failure, refractory status epilepticus, and prevention of awareness in patients treated with neuromuscular blocking agents. This review will focus on the remaining overwhelming majority of patients undergoing mechanical ventilation for whom the use of sedatives and analgesics should be minimized, with the goal that they be calm, lucid, pain-free, interactive, and cooperative with their care.