INTRODUCTION: Langerhans cell histiocytosis (LCH) is a heterogeneous disease, involving the accumulation of langerhans cells in various organs. The physician's perception of the disease varies considerably depending on their experience, the presentation of the disease or the short-term treatment outcome. As this disease is very rare, only a limited number of large surveys exist in the literature and many aspects of the management of patients remain obscure or controversial. AREAS COVERED: An expert opinion on the diagnosis and medical management of LCH is presented in this paper. The diagnostic procedures, including differential diagnosis, initial clinical workup and criteria for initiating therapy are reviewed, as well as disease evaluation criteria and therapeutic approaches. Controversial issues in the medical management of LCH patients (aged less than 18 years) are also briefly discussed. EXPERT OPINION: Further fundamental and clinical research is still needed in this field. Progress may be expected from collaborations organized at national and international levels, among collaborative groups and expert networks. Collections of tissue and blood samples in biobanks must also be organized. New international protocols will be opened to patient accrual and represent an opportunity to further develop global research.