Stratum corneum intercellular lipids play an important role in the regulation of skin water barrier homeostasis and water-holding capacity. Modification of intercellular lipid organization and composition may impair these properties. Patients with skin diseases such as atopic dermatitis, psoriasis, contact dermatitis, and some genetic disorders have diminished skin barrier function. Lipid composition in diseased skin is characterized by decreased levels of ceramide and altered ceramide profiles. To clarify mechanisms underlying ceramides as a causative factor of skin disease, investigators have examined the activity of enzymes in the stratum corneum on ceramide production and degradation. The activities of ceramidase, sphingomyelin deacylase, and glucosylceramide deacylase are increased in epidermal atopic dermatitis. Investigators have also compared the expression levels of sphingolipid activator protein in the epidermis of normal and diseased skin. A decreased level of prosaposin has been identified in both atopic dermatitis and psoriasis. These results indicate that decreased ceramide level is a major etiologic factor in skin diseases. Hence, topical skin lipid supplementation may provide opportunities for controlling ceramide deficiency and improving skin condition.