Monocytes and macrophages are key players in the immune system, with monocytes differentiating into macrophages in tissues based on environmental signals. Macrophages can adopt different functional phenotypes, such as M1 (pro-inflammatory) or M2 (anti-inflammatory), depending on their microenvironment. Monocytes can either die during inflammation or survive to become quiescent tissue macrophages or retain memory of their inflammatory activation. This review explores the differentiation of monocytes into macrophages, their functional roles in inflammation, and the relationship between monocytes and macrophages in different phases of inflammatory responses. Monocytes are circulating cells that originate from the bone marrow and can differentiate into tissue-resident macrophages or other cell types like dendritic cells. They are classified into three subsets based on surface markers: classical (CD14+), intermediate (CD14+CD16+), and non-classical (CD14-CD16+). These subsets have distinct functions, with classical monocytes being involved in inflammatory responses, while non-classical monocytes patrol blood vessels and monitor endothelial integrity. Tissue-resident macrophages can originate from embryonic progenitors or from circulating monocytes. Recent studies suggest that some tissue macrophages are derived from embryonic progenitors, while others are derived from monocytes. The self-renewal and proliferation of tissue-resident macrophages are regulated by factors like CSF-1 and GM-CSF. These macrophages play crucial roles in maintaining tissue homeostasis, clearing debris, and responding to pathogens. During inflammation, monocytes are recruited to tissues where they differentiate into macrophages. These macrophages can polarize into different functional phenotypes, such as M1 or M2, depending on the tissue environment. The plasticity of monocytes and macrophages allows them to adapt to different inflammatory conditions and contribute to tissue repair and resolution of inflammation. The recruitment of monocytes to tissues is regulated by chemokines like CCL2/CCR2 and CX3CL1/CX3CR1, which guide monocytes to sites of inflammation. The balance between monocyte-derived and tissue-resident macrophages is essential for maintaining tissue homeostasis and resolving inflammation.Monocytes and macrophages are key players in the immune system, with monocytes differentiating into macrophages in tissues based on environmental signals. Macrophages can adopt different functional phenotypes, such as M1 (pro-inflammatory) or M2 (anti-inflammatory), depending on their microenvironment. Monocytes can either die during inflammation or survive to become quiescent tissue macrophages or retain memory of their inflammatory activation. This review explores the differentiation of monocytes into macrophages, their functional roles in inflammation, and the relationship between monocytes and macrophages in different phases of inflammatory responses. Monocytes are circulating cells that originate from the bone marrow and can differentiate into tissue-resident macrophages or other cell types like dendritic cells. They are classified into three subsets based on surface markers: classical (CD14+), intermediate (CD14+CD16+), and non-classical (CD14-CD16+). These subsets have distinct functions, with classical monocytes being involved in inflammatory responses, while non-classical monocytes patrol blood vessels and monitor endothelial integrity. Tissue-resident macrophages can originate from embryonic progenitors or from circulating monocytes. Recent studies suggest that some tissue macrophages are derived from embryonic progenitors, while others are derived from monocytes. The self-renewal and proliferation of tissue-resident macrophages are regulated by factors like CSF-1 and GM-CSF. These macrophages play crucial roles in maintaining tissue homeostasis, clearing debris, and responding to pathogens. During inflammation, monocytes are recruited to tissues where they differentiate into macrophages. These macrophages can polarize into different functional phenotypes, such as M1 or M2, depending on the tissue environment. The plasticity of monocytes and macrophages allows them to adapt to different inflammatory conditions and contribute to tissue repair and resolution of inflammation. The recruitment of monocytes to tissues is regulated by chemokines like CCL2/CCR2 and CX3CL1/CX3CR1, which guide monocytes to sites of inflammation. The balance between monocyte-derived and tissue-resident macrophages is essential for maintaining tissue homeostasis and resolving inflammation.