Chronic neurodegenerative diseases represent major unmet needs for therapeutic interventions. Recently, the neurocentric view of brain function and disease has been challenged by a great number of evidence supporting the physiopathological potential of neuroglia. Astrocytes, in particular, play a pivotal role in brain homeostasis as they actively participate to neuronal metabolism, synaptic plasticity and neuroprotection. Furthermore, they are intrinsic components of brain responses to toxic and traumatic insults through complex processes involving several molecular and functional alterations that may lead to disruption of brain homeostasis and connectivity. This review provides a brief overview of current knowledge of astrocyte functions in the brain, and focus on some glial-specific pathways involved in astrocytic dysfunction that might be effective therapeutic targets for clinical management of neurodegenerative disorders.