The function of the lower urinary tract is storage and periodic elimination of urine. These functions are mediated by contractions of the smooth and striated muscle of the urethra and smooth muscle of the bladder, respectively, when stimulated by sympathetic and somatic efferent fibers to the urethra and parasympathetic efferent fibers to the bladder. The sympathetic efferent outflow along the hypogastric nerve to the urethral smooth muscle originates from the intermediate gray matter at the rostral lumbar spinal segments, while the somatic outflow along the pudendal nerve to the urethral striated muscle originates from a highly specialized motor cell group called Onuf’s nucleus located in the sacral spinal segments. The parasympathetic outflow along the pelvic nerve to the bladder smooth muscle originates from the sacral parasympathetic nucleus. The efferent activity to the urethra and bladder are regulated by “hardwired” neuronal reflex circuits organized spinally and supraspinally, respectively, that are triggered by activation of lightly-myelinated Aδ primary afferent fibers in the bladder and urethra. These “hardwired” storage and micturition reflexes are modulated by various neurotransmitters (e.g. serotonin, norepinephrine, opioids) that originate in various nuclei throughout the brain to coordinate micturition within behavioral and environmental contexts (Thor 2004). In addition to the urethra and bladder, spinal control of the pelvic floor (levator ani) muscle is also important for urine storage and voiding. The levator ani muscles are innervated by somatic α and γ motor neurons located in the sacral spinal cord with axons carried in the levator ani nerve (Barber et al, 2002). In animals, the levator ani motor neurons show strong dendritic projections into Onuf’s nucleus, suggesting an anatomical substrate for physiological coordination of urethral and pelvic floor striated muscles (Pierce et al, 2005). The sensory innervation of the pelvic floor muscles includes large myelinated axons associated with muscle spindles and Golgi tendon organs with spinal terminations in medial lamina VI, an area that contains interneurons involved in somatic stretch reflexes and which receives a strong dendritic projection from levator ani motor neurons. However, the vast majority of levator ani primary afferent neurons are small, peptidergic fibers (Pierce et al, 2006). Contraction of the bladder must be coordinated with relaxation of the urethra for voiding to occur. This synergy is accomplished by “turning off” or inhibiting the spinal sympathetic and somatic storage reflexes simultaneously with “turning on” or activating the supraspinal parasympathetic micturition reflex. Animal studies provide evidence for both supraspinal and spinal mechanisms for inhibiting the storage reflexes during periods of high bladder activity, with a strong focus on inhibitory interneurons in the lumbosacral dorsal commissure gray matter (Blok et al., 1998). This “spinal, urine-storage-reflex, inhibitory center”, or SUSRIC, becomes active when pelvic nerve afferent activity exceeds 5 – 10 Hz. The inhibition is activated within 50 msec of pelvic afferent nerve activation and lasts about 1,000 msec. SUSRIC receives input from both spinal and supraspinal neurons. Spinal damage in humans greatly compromises bladder-urethra synergy during voiding, which indicates a strong supraspinal component for synergy. Spinal damage, which severs supraspinal connection (i.e. destroying the supraspinal parasympathetic micturition reflex pathway), initially presents an areflexic bladder. However, in the weeks to months following spinal injury, a spinal parasympathetic micturition reflex pathway triggered by unmyelinated, C fiber primary afferent neurons develops (de Groat et al., 1990). Unfortunately, this spinal C fiber parasympathetic micturition reflex pathway is inefficient and poorly inhibits the storage reflexes, and patients present with high pressure bladders that predispose to renal failure and large post-void residual urine volumes that predispose to infection. Therefore, spinal cord injured patients generally depend on intermittent catheterization to empty the bladder. Understanding the neural circuits and transmitter systems involved in controlling the urethra and bladder offer opportunities for development of pharmacological, as well as device-based, therapies for incontinence and other voiding dysfunctions.