Endoneurial fibroblast-like cells (EFLCs) have been described for more than 60 years, but the embryology, functions, and pathology of these cells are not well defined. Several hypotheses of their origin have been proposed. A previous study suggesting that they were of neural crest origin is supported by our data in humans. This lineage might account for EFLCs having multiple biologic functions and involvement in pathological processes. Here, we review what is known about the origin; functions in collagen synthesis, phagocytosis, inflammatory responses, and immune surveillance; and the pathological alterations of EFLCs based on the literature and on our personal observations.