Cellular senescence, a state of permanent cell-cycle arrest accompanied by extensive epigenetic reprogramming and a pro-inflammatory secretome, has emerged as a pivotal mechanism in brain aging and the pathogenesis of neurodegenerative disorders. This chapter examines how diverse neural and glial populations, including neurons, astrocytes, microglia, and oligodendrocyte lineage cells, adopt senescence-like phenotypes marked by DNA damage responses, mitochondrial dysfunction, and chromatin remodeling. We review methods for detecting senescent cells in the central nervous system, from classic markers (p16INK4a, p21CIP1, SA-β-gal) to multi-omic signatures and advanced imaging probes. We then discuss the downstream consequences of senescence accumulation: sustained neuroinflammation, impaired neurogenesis and synaptic plasticity, and blood–brain barrier breakdown. The interplay between senescence and hallmark proteinopathies in Alzheimer’s, Parkinson’s, and amyotrophic lateral sclerosis is explored, highlighting bidirectional feedback loops that exacerbate tissue injury. Finally, we survey therapeutic approaches senolytics, senomorphics, anti-SASP agents, gene- and cell-based interventions, and lifestyle-based modulators before outlining challenges such as cell-type specificity, delivery across the blood–brain barrier, and distinguishing adaptive from pathological senescence. We propose future directions to refine biomarkers, enhance targeting precision, and integrate senescence-modulating treatments with neuroprotective strategies.