Aged epidermis develops an abnormality in permeability barrier homeostasis, which is accentuated further in photoaged skin. The biochemical basis is a global reduction in stratum corneum lipids and profound abnormality in cholesterol synthesis. Various cytokine/growth factor signaling pathways are abnormal in aged skin, particularly in the interleukin-1 family. Barrier repair therapy can be effective in restoring normal function if a cholesterol-dominant mixture of the three key physiologic lipids, including ceramides and free fatty acids, is emphasized.