A 25-year-old woman presenting with progressive muscle weakness in the distal extremities in the absence of sensory involvement for 2 years was diagnosed with multifocal motor neuropathy (MMN). Her disease was difficult to manage with various immunosuppressants, and the muscle weakness eventually progressed to involve the respiratory muscles, necessitating mechanical ventilation. Intravenous cyclophosphamide (CY) dramatically improved her symptoms, and she has since maintained her ambulatory status for 18 years with intermittent CY therapy. Because the patient presented with hemorrhagic cystitis due to CY, we also implemented mesna administration by bladder perfusion. The administration of CY should therefore be considered in patients with severe MMN that is unresponsive to standard therapy.