Publisher Summary Macrophage diseases have been one of the most vexing areas of histopathology during most of the twentieth century. While the terms “monocytes” and “macrophage” have been institutionalized among cell biologists, the term “histiocyte,” an obsolescent synonym for macrophage, is entrenched in the histopathologic description of macrophage diseases. Immunophenotyping, genotyping, and tracing lineages with cytogenetic markers were required to recognize the structural and functional disguises of the macrophage. Over the ensuing 20 years, clarification of the spectrum of the illness, the clinical manifestations of the different localized and generalized expression of the disease, and some improvements in management occurred. The immune accessory system includes at least two types of antigen-presenting or dendritic cells: one that presents antigen to B lymphocytes and another that presents antigen to T lymphocytes. The clinical course, prognosis, and need for therapy are influenced by the extent of the disease, the age of the patient, and the presence of liver, lung, or hematopoietic organ dysfunction. Allogeneic transplantation has been used to escalate therapeutic intensity. The diagnosis and management of macrophage disorders has been subject to idiosyncratic views of physicians, often based on a small number of cases.