The notion of our brain having a limited repertoire of cells to be used throughout our life has been refuted multiples times, showing systems by which new neurons are generated on demand, accounting for crucial aspects of brain function in a process known as neurogenesis. The potential of neurogenesis to replace lost neurons is enormous and has direct implications on how we understand the brain’s response to pathology. But replacing functional neurons is not trivial: an orchestrated sequence of steps is needed to ensure the timed generation of new cells, their migration to the sites of injury and their correct differentiation and integration into the pre-existing circuitry. However, there is evidence of this sequence being effective in replacing certain neuronal populations in brain disease. The perspective of understanding, manipulating and directing the brain’s self-repairing responses opens a vast avenue to explore novel therapeutic approaches to replace neuronal loss in neurodegenerative diseases.