Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of dendritic cells and the reticular cells. It is divided into single-system langerhans cell histiocytosis (SS-LCH) and multi-system langerhans cell system (MS-LCH). MS-LCH has a very poor prognosis. The key of survival is timely and effective treatment. The treatment protocols include chemotherapy, immunotherapy and stem cells transplantation. In this review, the new advances in the treatment of MS-LCH were systemically reviewed.