The S100 protein family consists of 25 members and share a common structure defined in part by the Ca2+ binding EF-hand motif. Multiple members' dysregulated expression is associated with progression, diagnosis and prognosis in a broad range of diseases, especially in tumors. They could exert wide range of functions both in intracellular and extracellular, including cell proliferation, cell differentiation, cell motility, enzyme activities, immune responses, cytoskeleton dynamics, Ca2+ homeostasis and angiogenesis. Gliomas are the most prevalent primary tumors of the brain and spinal cord with multiple subtypes that are diagnosed and classified based on histopathology. Up to now the role of several S100 proteins in gliomas have been explored. S100A8, S100A9 and S100B were highly expression in serum and may present as a marker correlated with survival and prognosis of glioma patients. Individual member was confirmed as a new regulator of glioma stem cells (GSCs) and a mediator of mesenchymal transition in glioblastoma (GBM). Additionally, several members up- or downregulation have been reported to involve in the development of glioma by interacting with signaling pathways and target proteins. Here we detail S100 proteins that are associated with glioma, and discuss their potential effects on progression, diagnosis and prognosis.