The article by Thomas A. Wynn and Kevin M. Vannella reviews the critical roles of macrophages in tissue repair, regeneration, and fibrosis. Macrophages, both resident tissue macrophages and recruited monocytes, undergo significant phenotypic and functional changes following tissue injury. These changes are essential for the initiation, maintenance, and resolution of the repair process. Disturbances in macrophage function can lead to aberrant repair, including uncontrolled inflammatory mediator and growth factor production, deficient anti-inflammatory macrophage generation, or impaired communication with other cell types, resulting in persistent injury and pathological fibrosis. The review highlights the mechanisms that guide macrophages to adopt various phenotypes, such as pro-inflammatory, pro-wound healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue regenerating. These phenotypes are crucial for different stages of tissue repair and can be therapeutic targets. For example, reducing the number of pro-inflammatory macrophages or boosting the activity of anti-inflammatory macrophages can improve tissue repair and reduce fibrosis. Recent studies have identified specific populations of macrophages, such as yolk sac-derived resident tissue macrophages and recruited monocytes, which play distinct roles in different organs. The review also discusses the protective roles of anti-inflammatory and anti-fibrotic macrophages, which are critical for the resolution of inflammatory and fibrotic responses. Therapeutic strategies that target macrophage function, such as modulating CSF1 signaling and altering macrophage transcription factors, are being explored to enhance tissue repair and prevent fibrosis. Finally, the article explores the role of macrophages in tissue regeneration, noting that they are essential for normal tissue homeostasis and organ regeneration. Macrophages provide critical signals for angiogenesis and tissue regeneration, and their interactions with stem cells and progenitor cells are crucial for successful regeneration.The article by Thomas A. Wynn and Kevin M. Vannella reviews the critical roles of macrophages in tissue repair, regeneration, and fibrosis. Macrophages, both resident tissue macrophages and recruited monocytes, undergo significant phenotypic and functional changes following tissue injury. These changes are essential for the initiation, maintenance, and resolution of the repair process. Disturbances in macrophage function can lead to aberrant repair, including uncontrolled inflammatory mediator and growth factor production, deficient anti-inflammatory macrophage generation, or impaired communication with other cell types, resulting in persistent injury and pathological fibrosis. The review highlights the mechanisms that guide macrophages to adopt various phenotypes, such as pro-inflammatory, pro-wound healing, pro-fibrotic, anti-inflammatory, anti-fibrotic, pro-resolving, and tissue regenerating. These phenotypes are crucial for different stages of tissue repair and can be therapeutic targets. For example, reducing the number of pro-inflammatory macrophages or boosting the activity of anti-inflammatory macrophages can improve tissue repair and reduce fibrosis. Recent studies have identified specific populations of macrophages, such as yolk sac-derived resident tissue macrophages and recruited monocytes, which play distinct roles in different organs. The review also discusses the protective roles of anti-inflammatory and anti-fibrotic macrophages, which are critical for the resolution of inflammatory and fibrotic responses. Therapeutic strategies that target macrophage function, such as modulating CSF1 signaling and altering macrophage transcription factors, are being explored to enhance tissue repair and prevent fibrosis. Finally, the article explores the role of macrophages in tissue regeneration, noting that they are essential for normal tissue homeostasis and organ regeneration. Macrophages provide critical signals for angiogenesis and tissue regeneration, and their interactions with stem cells and progenitor cells are crucial for successful regeneration.