The skin barrier, formed by the stratum corneum, envelops our bodies and provides an essential protective function. However, this barrier function differs between individuals due to biological variation. This variation arises as a result of inherited genetic variants, negative environmental or extrinsic factors, and age. A multitude of genetic changes determine a person's predisposition to a skin barrier defect and consequently their risk of developing a dry skin condition, such as atopic dermatitis. Extrinsic factors, including the weather and detrimental skin care practices, interact with these genetic changes to determine the severity of the defect and additively increase the risk of developing dry skin conditions. How these dry skin conditions present clinically, and how they persist and progress depends very much on a person's age. Understanding how the skin barrier varies between individuals, how it differs based on clinical presentation, and how it alters with age is important in developing optimum therapies to maintain healthy skin that provides the best protection.