Regulatory T (Treg) cells are known for their immunosuppressive functions in maintaining peripheral tolerance. Recent studies show that Treg cells also produce pro-repair mediators that are critical for tissue repair and regeneration. These mediators act on tissue-resident cells to initiate repair in a tissue-specific context. This review examines Treg cell interactions with tissue-resident non-immune cells in the context of tissue repair, fibrosis, and cancer, and discusses areas for future exploration. Treg cells modulate immune responses but also play critical roles in tissue repair and regeneration. They can protect tissue stem cell niches from inflammatory activity or directly signal non-immune tissue cells and/or stem cells. Treg cells promote tissue repair through immunosuppressive molecules that act on immune cells and tissue factors sensed by mesenchymal, epithelial, and endothelial cells. These interactions allow a common input to generate tissue-specific repair programs. Recent reviews have discussed Treg cell roles in various non-lymphoid tissues, but none have focused on how Treg cells communicate with other tissue cell types. This review examines interactions between Treg cells and epithelial, mesenchymal, or endothelial cells that mediate regeneration. Treg cell interactions with epithelial cells have been studied in multiple organ systems and disease states. For example, Treg cells promote tissue reparative processes in the lung and skin, and their interactions with epithelial cells are critical for regeneration. Treg cells also interact with mesenchymal cells in various tissues, including the lung, muscle, and cardiovascular system. These interactions are important for tissue repair and regeneration. Treg cells can influence mesenchymal cells through factors such as Areg, which promotes tissue repair. Treg cells also interact with endothelial cells, which are important for neovascularization in ischemic tissue models. Treg cells can "anchor" themselves in tissues, which promotes optimal interaction with tissue cells. Treg cells have been shown to influence mesenchymal cells in the brain and other tissues. Treg cell-derived factors such as Areg and IL-10 can promote tissue repair and regeneration. Treg cells can also be activated by damage-associated signals, such as IL-18 and IL-33, which promote Areg production. These signals drive the activation of Treg cell tissue repair programs. Treg cells can also be influenced by other tissue cell types, such as fibroblasts, which produce IL-33 and other mediators that influence Treg cell repair function. In chronic disease and cancer, Treg cells interact with fibroblasts and epithelial cells, which can be pro- or anti-fibrotic. Treg cells are enriched in the livers of mice and humans with chronic liver disease and interact with hepatic stellate cells, which are key to liver fibrosis. Treg cell depletion worsens liver and skin fibrosis,Regulatory T (Treg) cells are known for their immunosuppressive functions in maintaining peripheral tolerance. Recent studies show that Treg cells also produce pro-repair mediators that are critical for tissue repair and regeneration. These mediators act on tissue-resident cells to initiate repair in a tissue-specific context. This review examines Treg cell interactions with tissue-resident non-immune cells in the context of tissue repair, fibrosis, and cancer, and discusses areas for future exploration. Treg cells modulate immune responses but also play critical roles in tissue repair and regeneration. They can protect tissue stem cell niches from inflammatory activity or directly signal non-immune tissue cells and/or stem cells. Treg cells promote tissue repair through immunosuppressive molecules that act on immune cells and tissue factors sensed by mesenchymal, epithelial, and endothelial cells. These interactions allow a common input to generate tissue-specific repair programs. Recent reviews have discussed Treg cell roles in various non-lymphoid tissues, but none have focused on how Treg cells communicate with other tissue cell types. This review examines interactions between Treg cells and epithelial, mesenchymal, or endothelial cells that mediate regeneration. Treg cell interactions with epithelial cells have been studied in multiple organ systems and disease states. For example, Treg cells promote tissue reparative processes in the lung and skin, and their interactions with epithelial cells are critical for regeneration. Treg cells also interact with mesenchymal cells in various tissues, including the lung, muscle, and cardiovascular system. These interactions are important for tissue repair and regeneration. Treg cells can influence mesenchymal cells through factors such as Areg, which promotes tissue repair. Treg cells also interact with endothelial cells, which are important for neovascularization in ischemic tissue models. Treg cells can "anchor" themselves in tissues, which promotes optimal interaction with tissue cells. Treg cells have been shown to influence mesenchymal cells in the brain and other tissues. Treg cell-derived factors such as Areg and IL-10 can promote tissue repair and regeneration. Treg cells can also be activated by damage-associated signals, such as IL-18 and IL-33, which promote Areg production. These signals drive the activation of Treg cell tissue repair programs. Treg cells can also be influenced by other tissue cell types, such as fibroblasts, which produce IL-33 and other mediators that influence Treg cell repair function. In chronic disease and cancer, Treg cells interact with fibroblasts and epithelial cells, which can be pro- or anti-fibrotic. Treg cells are enriched in the livers of mice and humans with chronic liver disease and interact with hepatic stellate cells, which are key to liver fibrosis. Treg cell depletion worsens liver and skin fibrosis,