It has long been known that a large number of POMC-related peptides are found in skin. In this introduction I describe the formation of POMC-derived peptides in various tissues to indicate that processing is largely tissue-dependent. I focus on the peptides from the N-terminal fragment, such as gamma-MSH, ACTH and alpha-MSH, and beta-lipopropin as well as beta-endorphin. I touch on the factors that control the synthesis of the various peptides, which are now numerous and varied, and again are tissue specific. The biologic activity of the peptides generated from POMC are described in relation to their possible action in skin. In addition, I describe a new class of peptides induced in skin following injury and which are of great interest.