Neuronal circuits in the adult brain have long been viewed as static and stable. However, research in the past 20 years has shown that specialized regions of the adult brain, which harbor adult neural stem cells, continue to produce new neurons in a wide range of species. Brain plasticity is also observed after injury. Depending on the extent and permissive environment of neurogenic regions, different organisms show great variability in their capacity to replace lost neurons by endogenous neurogenesis. In Zebrafish and Drosophila, the formation of new neurons from progenitor cells in the adult brain was only discovered recently. Here, we compare properties of adult neural stem cells, their niches and regenerative responses from mammals to flies. Current models of brain injury have revealed that specific injury-induced genetic programs and comparison of neuronal fitness are implicated in brain repair. We highlight the potential of these recently implemented models of brain regeneration to identify novel regulators of stem cell activation and regenerative neurogenesis.