Many researchers consider the stratum corneum (SC) to be a “dead” tissue and most discussions on the SC barrier relate to its permeability characteristics. However, it is largely forgotten that the water lost through the tissue is essential for the functioning of a healthy and biologically very active SC.1 This imperfect and inbuilt water loss is the key in allowing hydration of the outer layers of the SC in order to maintain its flexibility, but more importantly to provide enough water to allow enzyme reactions that facilitate SC maturation events. One of these events, which is the subject of this chapter, is the aberration of the enzyme-mediated lysis of corneodesmosomes (CD) in the SC (corneodesmolysis) that would normally lead to desquamation of the SC but in this case leads to winter xerosis and the use of topical proteases to treat the condition. The key in precipitating the condition we call “dry skin” or cosmetic xerosis is perturbation of water gradients within the SC.2 Disruption of the natural moisture barrier leads to reduced proteolysis of key SC structural components called CD (Figure 17.1).3