The human mononuclear phagocyte network comprises dendritic cells (DCs), monocytes and macrophages with a range of immune functions including antigen presentation linking innate and adaptive immunity. A number of DC, monocyte and macrophage subsets have been described in lymphoid and non-lymphoid tissues of mouse and human, with increased understanding of their distinct functional properties and genetic and cellular pathways of development. More recently, through comparative biology studies, a unified nomenclature of mononuclear phagocytes has begun to emerge with the identification of homologous subsets in several species. In this review, we discuss the current classification of human mononuclear phagocytes and the parallel organization of this network in the mouse. We also review the genetic control and developmental pathway of human mononuclear phagocytes and the immunological functions of the distinct subsets in health and inflammation.