The bladder is an organ rich in vanilloid targets: dense unmyelinated c-fibers partially responsible for bladder sensation and response to noxious stimuli. Drugs such as capsaicin and resiniferatoxin (RTX) interact with the VR1 vanilloid receptor subtype to initially excite then subsequently desensitize the c-fibers. This chapter examines the literature describing the use of vanilloid receptor agonists in the treatment of the following urological disorders: neurogenic bladder (NGB), overactive bladder (OAB), and interstitial cystitis/painful bladder syndrome (IC/PBS). Review of the literature was performed using Pubmed and the following key words "capsaicin," "resiniferatoxin (RTX)," and "neurogenic bladder," "overactive bladder (OAB)," and "interstitial cystitis," "painful bladder syndrome." Articles focusing on randomized trials comparing intravesical administration of a vanilloid receptor agonist to placebo and those in English were reviewed. We conclude that capsaicin and RTX do appear to provide some acceptable treatment results in patients with neurogenic bladder, though larger studies are needed to confirm this. Although efficacy has been shown in some studies, currently the use of vanilloids cannot be recommended for routine use in patients with OAB as the need for catheterization may cause the risk to outweigh the benefit of treatment. Similarly, for the treatment of BPS, vanilloid receptor agonists lack strong evidence for efficacy or tolerability; larger studies are needed to define their role. Understanding how vanilloids are able to impact these disorders, however, may help further elucidate their underlying pathophysiological processes.