Many etiologies have been proposed for Langerhans cell histiocytosis (LCH). Recent scientific studies have clearly provided new insights into the etiology and pathogenesis of the disease. The possible role of viruses has not been completely negated, but no viral genomes have been consistently detected in LCH lesions. Other studies do not indicate that LCH arises from a primary defect in the immune system, although altered immune responses and immune dysfunction may play a role in the pathophysiology of the disease. Definitive results have been gained from molecular studies of clonality, however. These have definitively established that LCH is a clonal histiocytic disease rather than a reactive polyclonal disorder.