Abstract: Unlike regenerative-competent species that possess a remarkable intrinsic capacity to replenish lost neurons and restore neurocircuits spontaneously, the central nervous system in adult mammals lacks the ability to compensate for the neuronal loss caused by neurodegenerative diseases or traumatic injuries resulting in permanent loss of functionality. Inspired by earlier discoveries that radial glia or astrocytes isolated from the postnatal cortex can generate neurons, and fully differentiated somatic cells can be “reprogrammed” back to a pluripotent state driven by defined transcription factors, regenerative strategies to reprogram resident glial cells, such as astrocytes, Müller glia (MG), NG2-glia, and microglia, into neurons in vivo has emerged during the past decade. Theoretically, terminally differentiated cells could be converted from one fate to another using this strategy, especially when cells are lineage-related or originated from a common ancestor.