Since the first work about neuronal desensitization mediated by vanilloids, performed back in the 1970’s, major advances have been made in the elucidation of TRPV1 role in the genitourinary (GU) tract. The receptor distribution in the GU tract was unveiled. Both in vivo and in vitro studies brought new insights on TRPV1 physiology. The role of TRPV1 in bladder function in both normal and pathological states was clarified. All these data allowed the development of effective TRPV1 antagonists which not only confirmed the role of TRPV1 in micturition dysfunction but also suggested new approaches for the treatment of GU pathologies.