Proteoglycans are hybrid molecules composed of a core protein and covalently attached glycosaminoglycan chain(s). The structure, location, and processing of these molecules enables them to encode specific information that is used in multiple physiologic processes. Endothelial cells in the skin are influenced by proteoglycans through binding interactions between glycosaminoglycans and extracellular matrix, growth factors, cytokines, adhesion receptors, enzymes, and enzyme inhibitors. In wound repair, proteoglycans such as the syndecans are induced by antimicrobial peptides and can control growth factor responsiveness. The glycosaminoglycans further signal endothelial cells to increase expression of ICAM-1 and other molecules important for leukocyte adhesion. Thus, proteoglycans represent a powerful central regulatory element in skin that influences a wide variety of events and participates in host defense and tissue repair.