The roles of glycosaminoglycans and proteoglycans in the physiology of the urinary tract are reviewed. The structures of proteoglycans and glycosaminoglycans are reviewed together with their role in control of epithelial differentiation through stromal-epithelial interactions and as modulators of cytokines. Heparan sulfate proteoglycans appear to be important in maintaining selectivity of the kidney tubular basement membrane, and the majority of the glycosaminoglycan found in the urine appears to come from the upper tract. Evidence suggesting that a dense layer of glycosaminoglycans on the urothelial surface is important to maintaining urothelial impermeability is reviewed and new data showing a high density of proteoglycans on the lumenal surface of the urothelium is presented. The role of this layer in maintaining antibacterial adherence and impermeability was discussed together with data suggesting that failure of this layer is an etiologic factor in interstitial cystitis. A model of the bladder surface is also presented to illustrate the role of proteoglycans and exogenous glycosaminoglycans in the defenses of normal bladder lumen and the failure of these defenses in the interstitial cystitis bladder.