Langerhans-cell histiocytosis (LCH) is a rare disease characterized by a proliferation of bone marrow derived myeloid-dendritic cells. The accumulation of LCH cells results in a heterogeneous group of clinical presentations and a variable disease course ranging from spontaneous remissions to long-term debilitating disease, and may sometimes be mortal. Bone is the most common primary site of disease, but the other organs may be affected seriously, such as skin, liver, or lung. Many questions about LCH remain to be answered, including whether it is caused by a malignancy or by an immune system deficiency. The most recent data taken together swing the pendulum towards an immunologic aberration. Treatment modalities range from observation, surgical treatment of bone lesions, systemic or topical steroids, chemotherapy, and radiation therapy. Patients with multi-system organ dysfunction, and those with multiple reactivations of disease associated with permanent sequelae represent the greatest challenge. Due to the rarity of LCH in children and adults, patients should be treated in the experienced hospitals whenever possible to advance our knowledge of the optimal therapeutic strategies, and long-term outcomes.