Oncostatin M (OSM), a member of the interleukin-6 (IL-6) cytokine family, has yet to be well studied, especially in the context of the central nervous system (CNS). The biological functions of OSM are complex and variable, depending on the cellular microenvironment. Inflammatory responses and tumor development are among two of the major events that OSM is involved in. Although OSM levels remain low in the normal CNS, elevated expression occurs in pathological conditions. Therefore, it is crucial to understand the regulation of OSM to control its expression and/or its effects. Accumulating data demonstrate that OSM binds to specific receptor complexes, then activates two major signaling pathways: Janus Kinase-Signal Transducers and Activators of Transcription (JAK-STAT) and Mitogen-Activated Protein Kinase (MAPK), to regulate downstream events. In this review, we focus on the biological functions of OSM, the signaling pathways of OSM in the CNS, and OSM involvement in CNS diseases.