The urothelium, which lines the inner surface of the urinary bladder, is composed of at least three layers of cells: a basal cell layer attached to a basement membrane, an intermediate layer and a superficial apical layer with large hexagonal cells also known as umbrella cells. The region between the urothelium and the underlying smooth muscle layers is called the lamina propria and is richly supplied by blood vessels, nerves and myofibroblasts (or interstitial cells (IC)). In addition to being a barrier to urine, toxic metabolites and pathogens, the urothelium exhibits specialised sensory properties and functions as primary transducer of some mechanical and nociceptive stimuli. Three lines of evidence suggest that the urothelial cells participates in the detection of both physical and chemical stimuli: 1) close proximity to bladder nerves (efferent and afferent) 2) expression of numerous receptors/ion channels by urothelial cells such as purinergic, adrenergic and muscarinic receptors and transient receptor potential (TRP) channels and 3) secretion of chemical mediators such as neurotrophins, ATP, acetylcholine, prostaglandins etc. By receiving, amplifying, and transmitting information, the urothelium can convey information about the luminal pressure and urine composition to the nervous and muscular systems and help coordinate bladder function during filling and voiding. Defects in urothelial-cell signalling/barrier function are likely to contribute to the pathophysiology of bladder diseases. Alteration in tissue pH, mechanical or chemical trauma, bacterial infection, interstitial cystitis or spinal cord injury can result in altered expression/sensitivity of urothelial receptors/channels and enhanced release of chemical mediators such as nitric oxide (NO) and ATP from the urothelial cells. This may contribute to symptoms of urgency, frequency and pain during bladder filling and voiding. In addition, recent studies have shown that bladder urothelium expresses transmembrane channels called aquaporins (AQPs). AQPs regulate transepithelial water movement in various tissues e.g. kidney and are regulated by circulating vasopressin. We have also found the expression of AQPs in pig urinary bladder, a valuable alternative to human bladder for elucidating physiological principles. The discovery of AQPs in bladder urothelium supports a more controversial hypothesis that urothelium is able to modify composition and volume of urine in the lower urinary tract and may play an unappreciated but important role in water, salt and solute homeostasis. These observations open new exciting avenues for research in urothelial biology and could lead to new strategies for the clinical management of bladder-associated diseases.