The article discusses the origin and functions of tissue macrophages, highlighting that most adult tissue macrophages originate during embryonic development rather than from circulating monocytes. Each tissue has its own composition of embryonically derived and adult-derived macrophages, but it is unclear whether macrophages of distinct origins are functionally interchangeable or have unique roles at steady state. The article also discusses the role of circulating monocytes in inflammation and the tools used to identify the complex origin of tissue macrophages. It reviews the ontogeny and function of macrophages, emphasizing the importance of tissue niche versus ontological origin in regulating macrophage functions during steady state and inflammation. The article also discusses the development of macrophages during embryonic development, the role of transcription factors and surface markers in differentiating macrophages, and the use of genetic fate-mapping techniques to track macrophage populations. It highlights the importance of understanding the functions of different macrophage subsets and lineages in tissue homeostasis and disease. The article also discusses the role of macrophages in tissue repair and regeneration, the dynamics of monocyte and macrophage populations in tissues, and the importance of tissue-specific functions in macrophage regulation. The article concludes with the need for further research to understand the functions of different macrophage subsets and lineages in tissue homeostasis and disease.The article discusses the origin and functions of tissue macrophages, highlighting that most adult tissue macrophages originate during embryonic development rather than from circulating monocytes. Each tissue has its own composition of embryonically derived and adult-derived macrophages, but it is unclear whether macrophages of distinct origins are functionally interchangeable or have unique roles at steady state. The article also discusses the role of circulating monocytes in inflammation and the tools used to identify the complex origin of tissue macrophages. It reviews the ontogeny and function of macrophages, emphasizing the importance of tissue niche versus ontological origin in regulating macrophage functions during steady state and inflammation. The article also discusses the development of macrophages during embryonic development, the role of transcription factors and surface markers in differentiating macrophages, and the use of genetic fate-mapping techniques to track macrophage populations. It highlights the importance of understanding the functions of different macrophage subsets and lineages in tissue homeostasis and disease. The article also discusses the role of macrophages in tissue repair and regeneration, the dynamics of monocyte and macrophage populations in tissues, and the importance of tissue-specific functions in macrophage regulation. The article concludes with the need for further research to understand the functions of different macrophage subsets and lineages in tissue homeostasis and disease.