The skin works as an ultimate barrier between the body and the environment and protects the body not only against intrusion of biological, chemical, and physical agents but also against unusual loss of water. Many studies have been performed to elucidate the mechanism of the barrier function. Among the mammalian epidermal layers that, in order from the dermis to the surface of the skin, are composed of the stratum basal, stratum spinosum, stratum
granulosum, and stratum corneum (SC), the SC plays an important role in the barrier function. The SC consists of corneocytes filled with soft keratin and a matrix composed of intercellular lipids. Michaels et al.  have proposed a heterogeneous structural model of the SC, and later Elias  called it the “bricks and mortar” model, where “bricks” of corneocytes are embedded in a “mortar” of the intercellular lipid matrix, as shown schematically in Fig. 1.1. It has been widely accepted that most chemical agents penetrate through the intercellular lipid matrix, and they permeate mainly along the torturous pathway in the intercellular lamellar region. Consequently, the physical and chemical properties of the intercellular lipid matrix are an important subject in the studies on the function of the SC. As a result, many studies on the structural analysis of the SC have been concentrated in various kinds of SC model lipid systems [3, 4], where the lipids are mainly composed of ceramides, free fatty acids, and cholesterol in the SC. However, the detailed structure analysis of the SC is highly important in advance of studies on the SC lipid model systems, since the basic structures of the SC itself at the molecular level are not established yet. Therefore in this chapter I focus my attention to the structure of the SC at the molecular level studied by X-ray diffraction.