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This review highlights recent advances in cerebral microdialysis for investigational and clinical neurochemical monitoring in patients with critical neurological conditions.Use of microdialysis with other methods, including PET, electrophysiological monitoring and brain tissue oximetry in traumatic brain injury, subarachnoid hemorrhage with vasospasm, and infarction with refractory increased intracranial pressure have been reported. Potentially adverse neurochemical effects of nonconvulsive status epilepticus and cortical slow depolarization waves, both of which are increasingly recognized in traumatic brain injury and stroke patients, have been reported. The explosive growth in the use of cerebral oximetry with targeted management of brain tissue oxygen levels is leading to greater understanding of derangements of cerebral bioenergetics in the critically ill brain, but there remain unresolved basic issues. Understanding of the analytes that are measurable at the bedside – glucose, lactate, pyruvate, glutamate and glycerol – continues to evolve with glucose, lactate, pyruvate and the lactate–pyruvate ratio taking center stage. Analytes including inflammatory biomarkers such as cytokines and metabolites of nitric oxide are presently investigational, but hold promise for future application in advancing our understanding of basic pathophysiology, therapeutic target selection and prognostication. Growing consensus on indications for use of clinical microdialysis and advances in commercially available equipment continue to make microdialysis increasingly ‘ready for prime time.’Cerebral microdialysis is an established tool for neurochemical research in the ICU. This technique cannot be fruitfully used in isolation, but when combined with other monitoring methods provides unique insights into the biochemical and physiological derangements in the injured brain.