Cellular differentiation and tissue organization are defining features of metazoans. Unlike unicellular entities, multicellular organisms carry out physiologic functions through the concerted action of specialized cells assembled in discrete units; therefore, safeguarding the function of these units or tissues is of paramount importance to organismal homeostasis. Besides stromal and parenchymal cells, tissues harbor a significant population of recirculating and resident immune cells that include phagocytes, specialized antigen-presenting cells (APCs), and innate and adaptive lymphocytes. Regulatory T (Treg) cells, a specialized immunosuppressive lineage of the latter, have been shown to exert systemic effects on metabolism and partake in tissue repair, suggesting a dual role for adaptive lymphocytes in serving and protecting tissues. This review highlights the main mechanisms by which Treg cells support tissue function.