Normal bladder function is based on activation and maintenance of a sophisticated reflex mechanism involving sympathetic, parasympathetic, and somatic control of the lower urinary tract. The spinal and supraspinal neuronal pathways involved can be modulated by activation or inhibition of neurons in the periphery, at the lumbosacral and thoracolumbar spinal levels, and at supraspinal regulatory sites. Activation of the primary afferent neurons that innervate the lower urinary tract is the first step on this reflex pathway. Under conditions in which bladder function is compromised, abnormal activity in these afferent neurons can induce changes in these circuits, resulting in bladder dysfunction. Control and modulation of afferent pathways is a recent focus for the development of novel treatments for lower urinary tract disorders. This review focuses on the central regulation of bladder function by central serotonergic modulation of sensory pathways. Modulation of this monoaminergic system has dramatic effects on bladder activity and can be a target for pharmacologic treatment of bladder disorders.