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Astrocytes play crucial roles in central nervous system homeostasis, regulating neuronal and synaptic activity, modulating immune responses, and preserving the integrity of the blood-brain barrier. Recent genetic, transcriptomic, and proteomic studies have highlighted astrocytes as key players in the pathogenesis of neurodegenerative disorders. Yet, important questions remain unanswered: How are astrocyte functions changed across different neurodegenerative disorders? Does astrocyte reactivity contribute to neurodegenerative cascades? Can astrocyte-specific processes be targeted for therapy? This review summarizes recent findings on the potential contribution of astrocytes to disease onset and progression, with a focus on their therapeutic potential. It also explores the application of advanced omics technologies to unravel astrocyte complexity, along with the use of emerging murine models and human-induced pluripotent stem cells based systems to explore astrocyte involvement in disease mechanisms.