Macrophages are highly heterogeneous cells that can rapidly change their function in response to local microenvironmental signals. This review discusses the four stages of orderly inflammation mediated by macrophages: recruitment to tissues; differentiation and activation in situ; conversion to suppressive cells; and restoration of tissue homeostasis. It also discusses the protective and pathogenic functions of various macrophage subsets in antimicrobial defence, antitumour immune responses, metabolism and obesity, allergy and asthma, tumorigenesis, autoimmunity, atherosclerosis, fibrosis and wound healing. The review also briefly discusses the characterization of macrophage heterogeneity in humans. The mononuclear phagocytic system is generated from committed haematopoietic stem cells located in the bone marrow. Macrophage precursors are released into the circulation as monocytes, and within a few days they seed tissues throughout the body, including the spleen, which serves as a storage reservoir for immature monocytes. When monocytes migrate from the circulation and extravasate through the endothelium, they differentiate into macrophages or dendritic cells (DCs). Thus, the primary role of monocytes is to replenish the pool of tissue-resident macrophages and DCs in steady state and in response to inflammation. Monocytes, DCs and macrophages, along with neutrophils and mast cells, are 'professional' phagocytic cells. Professional phagocytes are distinguished from 'nonprofessional' phagocytes according to how effective they are at phagocytosis. A major factor that differentiates professional and non-professional phagocytes is that professional phagocytes express a multitude of receptors on their surfaces that detect signals that are not normally found in healthy tissues. The interplay between these receptors is likely to involve synergistic and antagonistic interactions, including downstream signalling mechanisms within the phagocytic cell that remain largely unknown. Within the mononuclear phagocyte pool, macrophages are often distinguished from DCs by differential expression of surface makers such as F4/80, CD11b and CD18, CD68 and Fc receptors. However, few, if any, known marker combinations can definitively segregate macrophages from myeloid DCs at present because these populations exist on a continuum of development from common myeloid progenitors. In this review, we provide an overview of the homeostatic, protective and pathogenic functions of the various macrophage subsets in health and disease, and discuss the current obstacles to the complete characterization of macrophage heterogeneity and effector function. Macrophages are divided into subpopulations based on their anatomical location and functional phenotype. Specialized tissue-resident macrophages include osteoclasts (bone), alveolar macrophages (lung), histiocytes (interstitial connective tissue) and Kupffer cells (Macrophages are highly heterogeneous cells that can rapidly change their function in response to local microenvironmental signals. This review discusses the four stages of orderly inflammation mediated by macrophages: recruitment to tissues; differentiation and activation in situ; conversion to suppressive cells; and restoration of tissue homeostasis. It also discusses the protective and pathogenic functions of various macrophage subsets in antimicrobial defence, antitumour immune responses, metabolism and obesity, allergy and asthma, tumorigenesis, autoimmunity, atherosclerosis, fibrosis and wound healing. The review also briefly discusses the characterization of macrophage heterogeneity in humans. The mononuclear phagocytic system is generated from committed haematopoietic stem cells located in the bone marrow. Macrophage precursors are released into the circulation as monocytes, and within a few days they seed tissues throughout the body, including the spleen, which serves as a storage reservoir for immature monocytes. When monocytes migrate from the circulation and extravasate through the endothelium, they differentiate into macrophages or dendritic cells (DCs). Thus, the primary role of monocytes is to replenish the pool of tissue-resident macrophages and DCs in steady state and in response to inflammation. Monocytes, DCs and macrophages, along with neutrophils and mast cells, are 'professional' phagocytic cells. Professional phagocytes are distinguished from 'nonprofessional' phagocytes according to how effective they are at phagocytosis. A major factor that differentiates professional and non-professional phagocytes is that professional phagocytes express a multitude of receptors on their surfaces that detect signals that are not normally found in healthy tissues. The interplay between these receptors is likely to involve synergistic and antagonistic interactions, including downstream signalling mechanisms within the phagocytic cell that remain largely unknown. Within the mononuclear phagocyte pool, macrophages are often distinguished from DCs by differential expression of surface makers such as F4/80, CD11b and CD18, CD68 and Fc receptors. However, few, if any, known marker combinations can definitively segregate macrophages from myeloid DCs at present because these populations exist on a continuum of development from common myeloid progenitors. In this review, we provide an overview of the homeostatic, protective and pathogenic functions of the various macrophage subsets in health and disease, and discuss the current obstacles to the complete characterization of macrophage heterogeneity and effector function. Macrophages are divided into subpopulations based on their anatomical location and functional phenotype. Specialized tissue-resident macrophages include osteoclasts (bone), alveolar macrophages (lung), histiocytes (interstitial connective tissue) and Kupffer cells (