Context: Current literature suggests that several pathophysiological factors and mechanisms might be responsible for the nonspecific symptom complex of overactive bladder (OAB).

Objective: To provide a comprehensive analysis of the potential pathophysiology underlying detrusor overactivity (DO) and OAB.

Evidence acquisition: A PubMed-based literature search was conducted in April 2018, to identify randomised controlled trials, prospective and retrospective series, animal model studies, and reviews.

Evidence synthesis: OAB is a nonspecific storage symptom complex with poorly defined pathophysiology. OAB was historically thought to be caused by DO, which was either "myogenic" (urgency initiated from autonomous contraction of the detrusor muscle) or "neurogenic" (urgency signalled from the central nervous system, which initiates a detrusor contraction). Patients with OAB are often found to not have objective evidence of DO on urodynamic studies; therefore, alternative mechanisms for the development of OAB have been postulated. Increasing evidence on the role of urothelium/suburothelium and bladder afferent signalling arose in the early 2000s, emphasising an afferent "urotheliogenic" hypothesis, namely, that urgency is initiated from the urothelium/suburothelium. The urethra has also recently been regarded as a possible afferent origin of OAB-the "urethrogenic" hypothesis. Several other pathophysiological factors have been implicated, including metabolic syndrome, affective disorders, sex hormone deficiency, urinary microbiota, gastrointestinal functional disorders, and subclinical autonomic nervous system dysfunctions. These various possible mechanisms should be considered as contributing to diagnostic and treatment algorithms.

Conclusions: There is a temptation to label OAB as "idiopathic" without obvious causation, given the poorly understood nature of its pathophysiology. OAB should be seen as a complex, multifactorial symptom syndrome, resulting from multiple potential pathophysiological mechanisms. Identification of the underlying causes on an individual basis may lead to the definition of OAB phenotypes, paving the way for personalised medical care.

Patient summary: Overactive bladder (OAB) is a storage symptom syndrome with multiple possible causes. Identification of the mechanisms causing a patient to experience OAB symptoms may help tailor treatment to individual patients and improve outcomes.