Scientific interest in defining the human body's ability to limit the effects of administered drugs and xenobiotics dates from the mid-19th century when developing knowledge and techniques in the field of organic chemistry first made such studies possible. The first experimental evidence documenting the existence of cytochrome p450 (CYP) dates to the year 1955, when an enzyme system capable of oxidizing xenobiotic compounds was identified in the endoplasmic reticulum of liver homogenates. From these days on several studies analyzed the expression and function of metabolizing phase I enzymes in liver cells. Due to the unique structural features of human skin, little was known about the expression and function of CYP enzymes in this tissue and their role in uptake, metabolism and elimination of xenobiotics as well as endogenous substrates. Lasting recent years it has become clear that human skin cells express various CYP enzymes, including CYP26AI which is responsible for the metabolism of retinoic acid in skin cells. It has been also shown that CYP enzyme expression patterns are cell type and tissue specific and that in skin cells this differs significantly from its expression in other environmental interfaces such as the liver, lung and gastrointestinal tract. Therefore knowledge of skin-specific CYP expression and function is a prerequisite for pharmacological studies of the skin.