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Abstract A recent study outlines the phenotypes of brain border region macrophages in developing, normal and glioblastoma‐affected brains. For the first time, the authors show in‐vivo turnover of human brain border macrophages. The findings have implications for the understanding of brain border immunity and potential macrophage targeting therapies. keypoints Human border region macrophages are distinct from microglia. These distinct phenotypes are established early during embryonal development ‐ Brain border macrophages are partially replaced by bone marrow‐derived myeloid cells. The transcriptional phenotypes of glioblastoma‐associated macrophage are determined by the anatomical region.