Significance: Proteoglycans have a distinct spatial localization in normal skin and are essential for the correct structural development, organization, hydration, and functional properties of this tissue. The extracellular matrix (ECM) is no longer considered to be just an inert supportive material but is a source of directive, spatial and temporal, contextual information to the cells via components such as the proteoglycans. There is a pressing need to improve our understanding of how these important molecules functionally interact with other matrix structures, cells and cellular mediators in normal skin and during wound healing. Recent Advances: New antibodies to glycosaminoglycan side chain components of skin proteoglycans have facilitated the elucidation of detailed localization patterns within skin. Other studies have revealed important proliferative activities of proteinase-generated fragments of proteoglycans and other ECM components (matricryptins). Knockout mice have further established the functional importance of skin proteoglycans in the assembly and homeostasis of the normal skin ECM. Critical Issues: Our comprehension of the molecular and structural complexity of skin as a complex, dynamic, constantly renewing, layered connective tissue is incomplete. The impact of changes in proteoglycans on skin pathology and the wound healing process is recognized as an important area of pathobiology and is an area of intense investigation. Future Directions: Advanced technology is allowing the development of new artificial skins. Recent knowledge on skin proteoglycans can be used to incorporate these molecules into useful adjunct therapies for wound healing and for maintenance of optimal tissue homeostasis in aging skin.