The article reviews the development and differentiation of monocytes, macrophages, and dendritic cells (DCs), which are crucial components of the immune system. Monocytes and macrophages play key roles in inflammation and innate immunity, while DCs initiate and regulate adaptive immune responses. Recent in vivo studies in mice have revealed new aspects of the developmental and lineage relationships among these cell types. Monocytes circulate in the blood and can differentiate into inflammatory DCs or macrophages during infection. Macrophages are resident phagocytic cells in tissues, involved in homeostasis and inflammation. DCs, specialized for antigen presentation, are divided into classical (cDCs) and plasmacytoid (PDCs) DCs, with distinct functions and developmental origins. The development of these cells is controlled by cytokines, particularly colony-stimulating factor 1 receptor (Csf1r) and fms-related tyrosine kinase 3 (Flt3). The article discusses the lineage relationships between monocytes, macrophages, and DCs, highlighting the role of transcription factors such as PU.1 in lineage commitment. It also addresses the challenges in understanding the replacement of macrophage subsets and resident cells, and the translation of findings from mouse models to human diseases.The article reviews the development and differentiation of monocytes, macrophages, and dendritic cells (DCs), which are crucial components of the immune system. Monocytes and macrophages play key roles in inflammation and innate immunity, while DCs initiate and regulate adaptive immune responses. Recent in vivo studies in mice have revealed new aspects of the developmental and lineage relationships among these cell types. Monocytes circulate in the blood and can differentiate into inflammatory DCs or macrophages during infection. Macrophages are resident phagocytic cells in tissues, involved in homeostasis and inflammation. DCs, specialized for antigen presentation, are divided into classical (cDCs) and plasmacytoid (PDCs) DCs, with distinct functions and developmental origins. The development of these cells is controlled by cytokines, particularly colony-stimulating factor 1 receptor (Csf1r) and fms-related tyrosine kinase 3 (Flt3). The article discusses the lineage relationships between monocytes, macrophages, and DCs, highlighting the role of transcription factors such as PU.1 in lineage commitment. It also addresses the challenges in understanding the replacement of macrophage subsets and resident cells, and the translation of findings from mouse models to human diseases.