Microglia, the resident immune cells of the central nervous system (CNS), play a crucial role in maintaining brain homeostasis and are implicated in various neurological diseases, including neurodegenerative and neuroautoimmune disorders. Activated microglia exhibit dysregulated neuroinflammation, contributing to neuronal damage and disease progression. Re-engineering microglia to treat neurological diseases is an emerging area of research. This review discusses the current developments in microglial engineering, including genetic targeting and therapeutic modulation. Genetic engineering techniques, such as viral transduction and CRISPR-Cas9, are used to alter gene expression in microglia, enabling them to deliver therapeutics to targeted sites and control neuroinflammation. Therapeutic modulation involves modifying microglial gene expression without altering their genetic composition, using nanoparticles and extracellular vesicles as delivery vehicles. The review highlights the potential of engineered microglia in treating conditions like glioblastoma, neurodegenerative diseases, and neuropsychiatric disorders. However, it also addresses the limitations of current techniques, including cell culture and animal models, and discusses future directions for improving the application of engineered microglia in neurological disease treatment.Microglia, the resident immune cells of the central nervous system (CNS), play a crucial role in maintaining brain homeostasis and are implicated in various neurological diseases, including neurodegenerative and neuroautoimmune disorders. Activated microglia exhibit dysregulated neuroinflammation, contributing to neuronal damage and disease progression. Re-engineering microglia to treat neurological diseases is an emerging area of research. This review discusses the current developments in microglial engineering, including genetic targeting and therapeutic modulation. Genetic engineering techniques, such as viral transduction and CRISPR-Cas9, are used to alter gene expression in microglia, enabling them to deliver therapeutics to targeted sites and control neuroinflammation. Therapeutic modulation involves modifying microglial gene expression without altering their genetic composition, using nanoparticles and extracellular vesicles as delivery vehicles. The review highlights the potential of engineered microglia in treating conditions like glioblastoma, neurodegenerative diseases, and neuropsychiatric disorders. However, it also addresses the limitations of current techniques, including cell culture and animal models, and discusses future directions for improving the application of engineered microglia in neurological disease treatment.