Overactive bladder (OAB) is a common condition. The International Continence Society defines OAB as a symptom complex characterized by urgency with or without urge incontinence, usually with frequency and nocturia. The first-line treatment for OAB includes behavioral therapy, such as caffeine reduction, fluid intake modification, weight reduction, bladder training, and pelvic floor muscle training, as well as treatment with antimuscarinic or β3 -adrenoceptor agonist medications. However, less than half of all cases achieve satisfactory outcomes following first-line treatment. Second-line therapy considered if satisfactory responses are not achieved after 8 to 12 weeks treatment with first-line therapy include intradetrusor botulinum toxin injection, neuromodulation, and surgical treatment. Patients with refractory OAB may have more severe symptoms or underlying pathophysiologies that were not resolved by the initial medication. The pathophysiologies of refractory OAB include occult neurogenic bladder, undetected bladder outlet obstruction, urethral-related OAB, urothelial dysfunction with aging, chronic bladder ischemia, chronic bladder inflammation, central sensitization, and autonomic dysfunction. This article discusses the possible pathophysiologies of refractory OAB. © 2019 John Wiley & Sons Australia, Ltd.