This article reviews the various investigative events that led to the endorsement of the term Langerhans cell histiocytosis for the various clinicopathologic conditions previously called Hand-Schüller-Christian disease, Abt-Letterer-Siwe disease, eosinophilic granuloma of bone, and histiocytosis X. The different denominations reflect the changing conceptual approaches to the so-called reticuloendothelial system and the successive acquisition of new ultrastructural and immunocytochemical data.