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In this article, the specific and general indications for sedatives in the neurocritical care unit are discussed, together with an overview on current insights in sedative protocols for these patients. In addition, physiological effects of sedative agents on the central nervous system are reviewed.In the general ICU population, a large body of evidence supports light protocolized sedation over indiscriminate deep sedation. Unfortunately, in patients with severe acute brain injury, the evidence from randomized controlled trials is scarce to nonexistent, and practice is supported by expert opinion, physiological studies and observational or small interventional trials. The different sedatives each have different beneficial effects and side-effects.Extrapolating the findings from studies in the general ICU population suggests to reserve deep continuous sedation in the neuro-ICU for specific indications. Although an improved understanding of cerebral physiological changes in patients with brain injury may be helpful to guide individualized sedation, we still lack the evidence base to make broad recommendations for specific patient groups.