Colony-stimulating factor 1 receptor (CSF1R) is essential for the production of microglia during embryogenesis, but its role in the adult brain is unknown. Here, the authors found that treatment of adult mice with CSF1R inhibitors resulted in the loss of almost all brain microglia, indicating a key role for this receptor in microglial homeostasis. Strikingly, removal of the inhibitors led to a rapid recovery of the microglial cell population. This effect was mediated through the proliferation and differentiation of nestin-positive cells, revealing these cells to be a microglial progenitor population in the adult brain.