Botulinum toxin has been at the center of attention in the last decades as a treatment option in several urologic diseases related to lower urinary tract function. Intravesical injection of the toxin is recommended for two main indications: neurogenic detrusor over-activity and idiopathic detrusor over-activity, resistant to oral therapy. In certain cases, clinical response to treatment is less than ideal, despite previous response. Defining the cause for a partial or no response is sometimes a challenge. In some patients, lack of response may be due to neutralizing antibodies against the toxin. The need for antibodies investigation in urologic patients is not well defined, as the management of a patient antibodies with further intra-vesical botulinum injections.