Substantial progress has been made regarding the elucidation of differentiation processes of the human hair follicle. This review first describes the genomic organization of the human hair keratin gene family and the complex expression characteristics of hair keratins in the hair-forming compartment. Sections describe the role and fate of hair keratins in the diseased hair follicle, particularly hereditary disorders and hair follicle-derived tumors. Also included is a report on the actual state of knowledge concerning the regulation of hair keratin expression. In the second part of this review, essentially the same principles are applied to outline more recent and, thus, occasionally fewer data on specialized epithelial keratins expressed in various tissue constituents of the external sheaths and the companion layer of the follicle. A closing outlook highlights issues that need to be explored further to deepen our insight into the biology and genetics of the hair follicle.