Recent work has made clear that heparan sulfate at the cell surface is essential for a wide variety of interactions of cells with their microenvironment, including the action of growth factors, extracellular matrix, proteases and protease inhibitors. A major source of this cell surface heparan sulfate is a multigene family of proteoglycans, the syndecans, that are expressed developmentally in association with changes in tissue organization and morphology and induced during wound repair. In this review, we describe mechanisms underlying the differential expression of the syndecans, focusing on syndecan-1. The induction of syndecan-1 can result from soluble extracellular factor(s) acting at multiple levels of cellular regulation. At the transcriptional level, the promoter of the murine syndecan-1 gene contains potential recognition sites for several well-known regulatory genes, including Hox and MyoD family members. Because changes in syndecan expression enable cells to become more or less responsive to their microenvironment, understanding these regulatory mechanisms can lead to an improved understanding of how cellular behavior is controlled during development and wound repair.