Multiple sclerosis is a neurologic disease caused by immune cell infiltration into the central nervous system, resulting in gray and white matter inflammation, progressive demyelination, and neuronal loss. Astrocytes, the most abundant cell population in the central nervous system (CNS), have been considered inert scaffold or housekeeping cells for many years. However, recently, it has become clear that this cell population actively modulates the immune response in the CNS at multiple levels. While being exposed to a plethora of cytokines during ongoing autoimmune inflammation, astrocytes modulate local CNS inflammation by secreting cytokines and chemokines, among other factors. This review article gives an overview of the most recent understanding about cytokine networks operational in astrocytes during autoimmune neuroinflammation and highlights potential targets for immunomodulatory therapies for multiple sclerosis.