Cells of the mononuclear phagocyte system (MPS) are found in large numbers in every organ of the body, where they contribute to innate and acquired immunity and homeostasis. This review considers the locations of MPS cells, surface markers that distinguish subsets of monocytes and macrophages, the pathways of MPS differentiation, and the growth factors and transcription factors that guide them. Although the number of MPS sub-populations that can be defined is infinite, the features that unite the MPS remain compelling. Those features clearly include antigen-presenting dendritic cells within the MPS and argue against any basis for separating them from macrophages.