Syndecans are multifunctional heparan sulfate proteoglycans (HSPGs) with roles in cell adhesion, migration, receptor trafficking and growth-factor interactions and signalling. Studies using syndecan null animals have revealed limited roles for syndecans during development; however, under conditions of challenge or insult, several phenotypes have emerged. Angiogenesis is an important process both in development and in wound healing, but also in pathologies such as cancer and chronic inflammatory conditions. In the present paper, we summarize the main studies elucidating the role of syndecans in angiogenesis and their potential as novel therapeutic targets.