Assessment of neurologic injury and the evolution of severe neurologic injury is limited in comatose or critically ill patients that lack a reliable neurologic examination.For common yet severe pathologies such as the comatose state after cardiac arrest,aneurysmal subarachnoid hemorrhage(aSAH),and severe traumatic brain injury(TBI),critical medical decisions are made on the basis of the neurologic injury.Decisions regarding active intensive care management,need for neurosurgical intervention,and withdrawal of care,depend on a reliable,high-quality assessment of the true state of neurologic injury,and have traditionally relied on limited assessments such as intracranial pressure monitoring and electroencephalogram.However,even within TBI there exists a spectrum of disease that is likely not captured by such limited monitoring and thus a more directed effort towards obtaining a more robust biophysical signature of the individual patient must be undertaken.In this review,multimodal monitoring including the most promising serum markers of neuronal injury,cerebral microdialysis,brain tissue oxygenation,and pressure reactivity index to access brain microenvironment will be discussed with their utility among specific pathologies that may help determine a more complete picture of the neurologic injury state for active intensive care management and long-term outcomes.Goaldirected therapy guided by a multi-modality approach appears to be superior to standard intracranial pressure(ICP)guided therapy and should be explored further across multiple pathologies.Future directions including the application of optogenetics to evaluate brain injury and recovery and even as an adjunct monitoring modality will also be discussed.