Langerhans cell histiocytosis (LCH) is a rare disease of the monocyte, macrophage, and dendritic cell lineage, but still the most common entity among the histiocytoses. Its clinical manifestations, severity, and clinical course are diverse and make diagnosis and management challenges. More than a century after its first description, LCH remains an intriguing disease. The disease results from somatic mutations leading to constitutive activation of the MAPK pathway. The most common causative mutation is the BRAF V600E, accounting for around 50-60% of the cases. Current experimental data suggest that LCH is myeloid neoplasia with inflammatory properties, yet the exact pathophysiology remains incompletely understood. The management concepts changed over time, closely reflecting the changing view on the nature of the disease process. Patients with single-system LCH (involvement of one organ system) generally have a favorable prognosis. The course of multisystem LCH is unpredictable upon diagnosis and requires systemic therapy. The international Histiocyte Society conducted three prospective clinical studies since the early 1990s. The standard front-line treatment for patients with multisystem LCH treated outside of controlled clinical trials consists of 6-12 weeks of initial therapy (daily oral steroids and weekly vinblastine injections), followed by pulses of prednisolone/vinblastine every three weeks, for a total treatment duration of 12 months. A currently ongoing study (LCH-IV) with a complex design (5 interventional and 2 observational strata) targets further reduction of mortality and morbidity by tailoring treatment intensity depending on expected risk. Accumulating knowledge on LCH pathobiology opens chances for molecular markers and targeted therapy.