Macrophages reside within the diverse anatomical compartments of the central nervous system (CNS). Within each compartment, these phagocytes are exposed to unique combinations of niche signals and mechanical stimuli that instruct their tissue-specific identities. Whereas most CNS macrophages are tissue-embedded, the macrophages of the cerebrospinal fluid (CSF) system are bathed in an oscillating liquid. Studies using multiomics technologies have recently uncovered the transcriptomic and proteomic profiles of CSF macrophages, enhancing our understanding of their cellular characteristics in both rodents and humans. Here, we review the relationships between CNS macrophage populations, with a focus on the origins, phenotypes, and functions of CSF macrophages in health and disease.