The connective tissue of any organ in the body is generally referred to as stroma. This complex network is commonly composed of leukocytes, extracellular matrix components, mesenchymal cells and a collection of nerves, blood and lymphoid vessels. Once viewed primarily as a structural entity, stromal cells of mesenchymal origin are now being intensely examined for their ability to directly regulate various components of immune cell function. There is particular interest in the ability of stromal cells to influence the homeostasis, activation and proliferation of T lymphocytes. One example of this regulation occurs in the lymph node (LN) where fibroblastic reticular cells (FRCs) support the maintenance of naïve T cells, induce antigen-specific tolerance and restrict the expansion of newly activated T cells. In an effort to highlight the varied immunoregulatory properties of FRCs, we have reviewed the most recent advances in this field and provide some insights into potential future directions.