Proteoglycans regulate cell behavior through interactions of their core proteins and glycosaminoglycans with extracellular matrix proteins, growth factors and chemokines. Changes in proteoglycans occur in the tumor microenvironment, but the consequences of those changes are not well understood. Here, Edwards discusses proteoglycans studied in prostate cancer, considering their roles in tumor progression and how cancers use changes in proteoglycans to promote their own survival, growth and spread.