Syndecans are a four member family of multifunctional transmembrane heparan sulphate bearing cell surface receptors. Each family member has common molecular architecture but a distinct expression profile. Numerous molecular interactions between syndecan heparan sulphate chains, growth factors, cytokines, and extracellular matrix molecules have been reported and syndecans are intimately associated with cell adhesion and migration. Here, we describe the important emerging concept that contained within syndecan extracellular core proteins are "adhesion regulatory domains." Cell adhesion is driven by the integrins and syndecan ectodomain adhesion regulatory domains can alter integrin driven cellular responses. Cell adhesion and migration is central to numerous pathologies and an understanding of how syndecan ectodomains influence integrins will lead to novel therapeutic strategies.