ObjectiveTo review current knowledge of the pathophysiology of otosclerosis and to review hypotheses for the amelioration of this disease.Data SourcesReview of the literature and experimental observations by the authors.ConclusionsOtosclerosis is a localized disease of bone remodeling within the otic capsule of the human temporal bone. Unlike other similar bone diseases, it does not occur outside of the temporal bone. These lesions seem to begin by resorption of stable otic capsule bone in adults, followed by a reparative phase with bone deposition. There are clearly genetic factors that lead to this disease, but measles virus infection and autoimmunity also may play contributing roles. Surgical correction of the conductive hearing loss is highly effective, but nonsurgical intervention has not yet been shown to prevent or slow the disease. Of the factors that may inhibit this process, fluorides, cytokine inhibitors, and bisphosphonates, third-generation bisphosphonates appear to hold the most promise.