Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia characterized by accumulation of clonal CD1a-positive immature dendritic cells (LCH cells) accompanied by infiltration of various inflammatory cells such as eosinophils, lymphocytes, macrophages, and osteoclast-like multinuclear giant cells. Mutually exclusive oncogenic mutations in genes involved in the mitogen-activated protein kinase (MAPK) signaling pathway, such as BRAF and MAP2K1, are detected in LCH cells from more than two thirds of LCH patients, suggesting that LCH cells are neoplastic. Proinflammatory cytokines and chemokines play a role in the clinical presentation of LCH, indicating that LCH is also an inflammatory disorder. Several major issues regarding the treatment of childhood LCH remain: how do clinicians rescue patients with risk-organ involvement that do not respond to first-line therapy, and how do they reduce and treat central nervous system-related consequences such as central diabetes insipidus and neurodegeneration? More research is needed to resolve these treatment-related issues.