Multidisciplinary research over decades has brought significant understanding of hair and its components from the macromolecular structure to the keratin genes. The cuticle of the hair has important influences on the properties of hair, be it care of human hair or textile applications of wool. Research has elicited some of the structural features of cuticle cells but major gaps remain. The basis of resistance of cuticle cells to chemical and physical degradation has been ascribed mainly to two proteins, KAP5 and KAP10, and to disulphide bonds, as well as the surface epicuticle and isopeptide bonding. The epicuticle, about 10nm thick, is a layer on the outermost surface of the cuticle. The KAP 5 and 10 proteins have been localised to the exocuticle by immunoelectron microscopy and by mass spectrometric identification in cuticle cell membranes isolated from wool. Keratin IFs have been localised to the cuticle although filaments per se have not been observed by electron microscopy (TEM). The endocuticle contains proteins that are not compacted and is not as physically tough as the exocuticle; a S100 protein has been identified in the endocuticle. The basis of the hydrophobic properties of hair is known to be fatty acids of which about half is the anteiso 18-methyleiocosanoic acid, covalently bonded to a protein or proteins on the outermost surface. TEM studies of aberrant human hair from subjects with maple syrup urine disease (MSUD) was important in demonstrating that only the upper surface of all cuticle cells is where the fatty acids are located. The protein(s) to which the fatty acids are attached are unknown. Surveys of proteins in membranous residues from hair suggest that the KAPs are candidates. Claims that involucrin or loricrin could be involved have not been substantiated. New approaches that retain the protein-lipid linkages can be used to investigate some of these issues.