(A) Monocytes are recruited to the tissue during injury, where they differentiate into macrophages in response to cues provided by the injured microenvironment. We propose two models to understand the distinct roles of monocytes in promoting tissue injury and tissue repair during injury resolution, which are not mutually exclusive. In the passive repair model (top panel), tissue regeneration restores signals that promote macrophage differentiation into cells that increasingly resemble tissue-resident macrophages. As the homeostatic function of macrophages is restored, tissue repair is accelerated, creating a feed-forward loop that restores homeostasis. In the active repair model (bottom panel), monocyte-derived macrophages respond to cues in their microenvironment and express or secrete factors that drive tissue repair. Interactions include the uptake of apoptotic cells (often neutrophils), regulatory T cells, pathogens, and epithelial cells. These monocyte-derived macrophages might promote the resolution of inflammation through secretion of antiinflammatory and pro-repair mediators including metabolic intermediates, pro-resolution lipid mediators, antiinflammatory cytokines, and matrix remodeling proteins. (B) The kinetics of monocyte-derived macrophage recruitment to tissues is a subject of active investigation. A single wave of monocytes may enter during injury and be progressively reshaped into pro-resolving macrophages in response to cues within the local microenvironment (top panel). Alternatively, distinct waves of monocyte-derived macrophages might be involved in tissue injury (red) and tissue repair (purple) (middle panel), or monocytes with varying functions might be continuously recruited over the course of tissue injury and repair (bottom panel).