A 14-year-old boy with longstanding multisystem Langerhans cell histiocytosis (LCH) had multifocal bone pain unresponsive to chemotherapy, corticosteroids, anti-inflammatories, and narcotic analgesics. He responded to two cycles of intravenous pamidronate, each 90 mg per day on three consecutive days. Two subsequent episodes of deterioration also responded to treatment. The pathophysiology of his bone pain and the likely mechanisms of biphosphonate action are discussed, with emphasis on the molecular and cellular basis of LCH.