Neurocritical care is an important branch of critical care medicine. Neurocritical care patients characterize with poor prognosis, ie. high mortality and high disability rate.S100 calcium binding protein B (S100B) is a protein biomarker mainly distributed in astrocytes of brain. Previous studies have shown that abnormal expression and distribution of S100B were significantly associated with the progression and prognosis of serveral neurocritical care diseases such as severe traumatic brain injury, stroke, sepsis-associated encephalopathy, hypoxie-ischemic encephalopathy, and central nervous system infection. The detection of S100B may valuable in the early identification and severity assessment of neurological injury, and in screening patients with poor prognosis and long-term disability risk for early intervention. Targeting S100B may be a potential target for future brain-protective therapy in neurocritical care patients. This article reviews the clinical and basic research progress of S100B in the field of severe neurological diseases, in order to provide guidance for the subsequent research work.