The inner root sheath (IRS) is an important structure of the lower part of the hair follicle that surrounds and protects the growing hair. The inner root sheath (IRS) of human hair follicles consists of three concentric cell layers; the cuticle, Huxley’s layer, and Henle’s layer. The peripheral mass of matrix cells in the hair bulb are the basis which form all three layers. The formation of the IRS during mammalian epidermis evolutions allowed the physiological exit of hairs present inside the skin. Its dimension and curvature largely determines the shape of the hair. IRS express specific type II epithelial keratins and a unique fibroblast growth factor (FGF). Both of proteins have a preferential role in hair development.