Microglia, the resident immune cells of the central nervous system (CNS), play a crucial role in maintaining homeostasis by clearing cellular debris through phagocytosis. This process is essential for tissue repair and regeneration following CNS injury. Recent studies highlight that microglial phagocytosis not only removes debris but also promotes neuronal circuit reorganization and repair. In neurodegenerative diseases and aging, impaired microglial function leads to inadequate regeneration. Understanding microglial mechanisms is vital for developing therapies to enhance CNS repair. Microglia are highly motile, constantly surveying the CNS environment and responding to injury by migrating to affected areas. They clear debris, release trophic factors, and produce anti-inflammatory cytokines, which support neuronal survival and myelin repair. Phagocytic receptors such as TREM2 and complement receptors are critical for efficient debris clearance. Deficiencies in these receptors, as seen in mutations, lead to neurodegenerative diseases. In conditions like multiple sclerosis and Alzheimer's disease, microglia can either be harmful or beneficial, depending on their activation state. In multiple sclerosis, microglial phagocytosis of myelin debris is essential for remyelination, while in Alzheimer's, microglia can clear amyloid-beta plaques or contribute to neurotoxicity. Ageing reduces microglial function, impairing debris clearance and regeneration. Microglial phagocytosis is vital for axon regeneration, as seen in models of Wallerian degeneration. Efficient clearance of myelin debris allows for effective remyelination and axon repair. In Alzheimer's, microglial clearance of amyloid-beta plaques is crucial for preventing neurodegeneration. However, in some cases, microglia may fail to clear debris, leading to chronic disease progression. In summary, microglial phagocytosis is a key mechanism for CNS homeostasis and regeneration. Enhancing this function through therapeutic strategies targeting microglial receptors and signaling pathways could improve recovery from CNS injuries and diseases.Microglia, the resident immune cells of the central nervous system (CNS), play a crucial role in maintaining homeostasis by clearing cellular debris through phagocytosis. This process is essential for tissue repair and regeneration following CNS injury. Recent studies highlight that microglial phagocytosis not only removes debris but also promotes neuronal circuit reorganization and repair. In neurodegenerative diseases and aging, impaired microglial function leads to inadequate regeneration. Understanding microglial mechanisms is vital for developing therapies to enhance CNS repair. Microglia are highly motile, constantly surveying the CNS environment and responding to injury by migrating to affected areas. They clear debris, release trophic factors, and produce anti-inflammatory cytokines, which support neuronal survival and myelin repair. Phagocytic receptors such as TREM2 and complement receptors are critical for efficient debris clearance. Deficiencies in these receptors, as seen in mutations, lead to neurodegenerative diseases. In conditions like multiple sclerosis and Alzheimer's disease, microglia can either be harmful or beneficial, depending on their activation state. In multiple sclerosis, microglial phagocytosis of myelin debris is essential for remyelination, while in Alzheimer's, microglia can clear amyloid-beta plaques or contribute to neurotoxicity. Ageing reduces microglial function, impairing debris clearance and regeneration. Microglial phagocytosis is vital for axon regeneration, as seen in models of Wallerian degeneration. Efficient clearance of myelin debris allows for effective remyelination and axon repair. In Alzheimer's, microglial clearance of amyloid-beta plaques is crucial for preventing neurodegeneration. However, in some cases, microglia may fail to clear debris, leading to chronic disease progression. In summary, microglial phagocytosis is a key mechanism for CNS homeostasis and regeneration. Enhancing this function through therapeutic strategies targeting microglial receptors and signaling pathways could improve recovery from CNS injuries and diseases.