Langerhans cell histiocytosis (LCH) is a disorder of dendritic cell proliferation with subsequent tissue damage often requiring chemotherapy. Neurodegenerative LCH presents with neuromuscular, cognitive, and behavioral alterations typically occurring years after diagnosis of active LCH. We present a male child with a 4-year history of growth arrest, polyuria, polydipsia, recurrent otitis media, and seborrheic dermatitis. Cutaneous biopsies confirmed LCH and chemotherapy was initiated. During treatment for active LCH he developed neuropsychiatric decline. White matter changes on brain MRI were consistent with neurodegenerative LCH. Treatment was changed to cytarabine and intravenous immunoglobulin. After 1 year of therapy the patient experienced neuropsychological improvement.