The article by Italiani and Boraschi reviews the differentiation and function of monocytes and macrophages, highlighting the complex interplay between these cells in both homeostasis and inflammation. Monocytes, circulating in the blood, bone marrow, and spleen, are key players in the innate immune response, capable of phagocytosis, production of reactive oxygen species, and cytokine secretion. They are recruited to tissues during inflammation and can differentiate into macrophages. The article discusses the heterogeneity of monocytes, particularly the three functional subsets (classical, intermediate, and non-classical), and their roles in different tissues. It also explores the origin of tissue-resident macrophages, questioning the traditional view that they derive primarily from circulating monocytes. Instead, it suggests that macrophages may arise from embryonic progenitors or self-renew through local proliferation. The review further examines the plasticity of monocytes and macrophages during inflammation, including their recruitment, proliferation, and polarization into different functional phenotypes (M1 and M2). The authors emphasize the importance of growth factors like CSF-1 and IL-34 in regulating monocyte and macrophage development and function, and discuss the implications of these findings for understanding immune responses and diseases.The article by Italiani and Boraschi reviews the differentiation and function of monocytes and macrophages, highlighting the complex interplay between these cells in both homeostasis and inflammation. Monocytes, circulating in the blood, bone marrow, and spleen, are key players in the innate immune response, capable of phagocytosis, production of reactive oxygen species, and cytokine secretion. They are recruited to tissues during inflammation and can differentiate into macrophages. The article discusses the heterogeneity of monocytes, particularly the three functional subsets (classical, intermediate, and non-classical), and their roles in different tissues. It also explores the origin of tissue-resident macrophages, questioning the traditional view that they derive primarily from circulating monocytes. Instead, it suggests that macrophages may arise from embryonic progenitors or self-renew through local proliferation. The review further examines the plasticity of monocytes and macrophages during inflammation, including their recruitment, proliferation, and polarization into different functional phenotypes (M1 and M2). The authors emphasize the importance of growth factors like CSF-1 and IL-34 in regulating monocyte and macrophage development and function, and discuss the implications of these findings for understanding immune responses and diseases.