Intravesical agents for overactive bladder have mostly been used in patients with neurogenic bladder disorders. The patients have usually had severe detrusor hyperreflexia (DH) plus a disorder of bladder emptying, and because of residual urine have been performing intermittent self-catheterization. Intravesical medication has therefore been appropriate. Strategies for treating DH have been either to lessen the parasympathetic efferent activity or to de-afferent the bladder. Two types of treatment have been used: intravesical medications that block pelvic nerve-detrusor smooth muscle cholinergic transmission, or agents that block the afferent arm of the reflex that causes detrusor contraction. Intravesical oxybutynin is thought to have some local anesthetic effect, although its main mode of action is to block cholinergic transmission. It has been demonstrated to be effective in resistant DH. Intravesical atropine has been demonstrated to increase bladder capacity but its usefulness in the clinical management of DH has yet to be demonstrated. Local anesthetics can increase bladder capacity, but the effect is short-lived. Longer-acting agents may have a selective neurotoxic effect on capsaicin-sensitive bladder afferents. Many patients worldwide have now been treated with intravesical capsaicin. Resiniferatoxin (RTX) is an ultrapotent capsaicin analog that has the significant advantage of being a nonirritant. Intravesical agents appear to be attractive alternatives to oral medication and hold the exciting possibility of selectively targeting end organs implicated in pathophysiologic responses.