The urothelium was once purported to be a passive membrane. However, a growing body of evidence indicates that the urothelium actively participates in sensory functions, expressing various receptors and ion channels, as well as releasing neurotransmitters in response to stimuli. Vanilloid receptors, P2X₃ purinergic receptors, adenosine triphosphate, nitric oxide, and acetylcholine have been implicated in urothelial–neuronal interactions. Substances released from urothelial cells can alter the excitability of bladder afferent nerves acutely and chronically; these observations appear to be of particular importance in chronic bladder conditions and in the aging bladder. Evidence suggests that the involvement of the muscarinic receptor in bladder function extends beyond detrusor contractility and into afferent sensory functioning. These observations have significant implications for a more complete understanding of the effects of currently used drugs on these sensory mechanisms and for identifying potential targets for pharmacologic intervention in bladder disorders.