Macrophages play a central role in atherosclerosis, with their quantity and phenotype influencing both disease progression and regression. Atherosclerosis is a chronic inflammatory disease driven by lipid metabolism imbalance and a maladaptive immune response, characterized by the accumulation of cholesterol-laden macrophages in the arterial wall. These macrophages, typically classified as foam cells, contribute to plaque progression by secreting pro-inflammatory mediators and promoting inflammation. However, macrophage clearance of lipoproteins is initially beneficial, but their excessive lipid accumulation leads to dysregulated lipid metabolism and compromised immune functions. Macrophages in atherosclerotic plaques have reduced migratory capacity, contributing to inflammation and plaque progression. Advanced plaques involve other immune cells and vascular smooth muscle cells in the inflammatory process. Dying macrophages release lipid contents and tissue factor, forming a pro-thrombotic necrotic core, a key component of unstable plaques that can rupture, leading to myocardial infarction or stroke. Hypercholesterolemia increases circulating monocytes, particularly the inflammatory LY6C^hi subset, which are recruited to atherosclerotic plaques. Monocyte recruitment involves multiple steps, including capture, rolling, and transmigration, regulated by chemokines and adhesion molecules. Chemokine receptor-chemokine pairs such as CCR2–CCL2, CX3CR1–CX3CR1, and CCR5–CCL5 are critical for monocyte transmigration. Neuronal guidance cues also play a role in monocyte recruitment and macrophage chemostasis. Lipoprotein uptake by macrophages leads to foam cell formation, a key step in atherosclerosis. Modified LDL, recognized by scavenger receptors, is internalized by macrophages, leading to cholesterol accumulation. Multiple pathways contribute to foam cell formation, including scavenger receptor-mediated uptake and pinocytosis. Defective cholesterol trafficking in macrophages can lead to ER stress and apoptosis, contributing to plaque instability. Lipid efflux pathways, such as ABCA1 and ABCG1, help remove cholesterol from macrophages, reducing inflammation. Autophagy also plays a role in macrophage cholesterol efflux and immune responses. Innate immune activation, including NLRP3 inflammasome activation and TLR signaling, contributes to atherosclerosis. Oxidized LDL and other ligands trigger TLR signaling, leading to inflammation and plaque progression. Macrophage polarization into M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes influences plaque inflammation and resolution. M1 macrophages secrete pro-inflammatory cytokines, while M2 macrophages promote tissue repair and efferocytosis. Therapeutic strategies targeting macrophage polarization, efferocytosis, and emigration may help reduce atherosclerosis. Factors such as IL-13 promote M2 macrophMacrophages play a central role in atherosclerosis, with their quantity and phenotype influencing both disease progression and regression. Atherosclerosis is a chronic inflammatory disease driven by lipid metabolism imbalance and a maladaptive immune response, characterized by the accumulation of cholesterol-laden macrophages in the arterial wall. These macrophages, typically classified as foam cells, contribute to plaque progression by secreting pro-inflammatory mediators and promoting inflammation. However, macrophage clearance of lipoproteins is initially beneficial, but their excessive lipid accumulation leads to dysregulated lipid metabolism and compromised immune functions. Macrophages in atherosclerotic plaques have reduced migratory capacity, contributing to inflammation and plaque progression. Advanced plaques involve other immune cells and vascular smooth muscle cells in the inflammatory process. Dying macrophages release lipid contents and tissue factor, forming a pro-thrombotic necrotic core, a key component of unstable plaques that can rupture, leading to myocardial infarction or stroke. Hypercholesterolemia increases circulating monocytes, particularly the inflammatory LY6C^hi subset, which are recruited to atherosclerotic plaques. Monocyte recruitment involves multiple steps, including capture, rolling, and transmigration, regulated by chemokines and adhesion molecules. Chemokine receptor-chemokine pairs such as CCR2–CCL2, CX3CR1–CX3CR1, and CCR5–CCL5 are critical for monocyte transmigration. Neuronal guidance cues also play a role in monocyte recruitment and macrophage chemostasis. Lipoprotein uptake by macrophages leads to foam cell formation, a key step in atherosclerosis. Modified LDL, recognized by scavenger receptors, is internalized by macrophages, leading to cholesterol accumulation. Multiple pathways contribute to foam cell formation, including scavenger receptor-mediated uptake and pinocytosis. Defective cholesterol trafficking in macrophages can lead to ER stress and apoptosis, contributing to plaque instability. Lipid efflux pathways, such as ABCA1 and ABCG1, help remove cholesterol from macrophages, reducing inflammation. Autophagy also plays a role in macrophage cholesterol efflux and immune responses. Innate immune activation, including NLRP3 inflammasome activation and TLR signaling, contributes to atherosclerosis. Oxidized LDL and other ligands trigger TLR signaling, leading to inflammation and plaque progression. Macrophage polarization into M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes influences plaque inflammation and resolution. M1 macrophages secrete pro-inflammatory cytokines, while M2 macrophages promote tissue repair and efferocytosis. Therapeutic strategies targeting macrophage polarization, efferocytosis, and emigration may help reduce atherosclerosis. Factors such as IL-13 promote M2 macroph