Stromal cells are a subject of rapidly growing immunological interest based on their ability to influence virtually all aspects of innate and adaptive immunity. Present in every bodily tissue, stromal cells complement the functions of classical immune cells by sensing pathogens and tissue damage, coordinating leukocyte recruitment and function, and promoting immune response resolution and tissue repair. These diverse roles come with a price: like classical immune cells, inappropriate stromal cell behavior can lead to various forms of pathology, including inflammatory disease, tissue fibrosis, and cancer. An important immunological function of stromal cells is to act as information relays, responding to leukocyte-derived signals and instructing leukocyte behavior in kind. In this regard, several members of the interleukin-6 (IL-6) cytokine family, including IL-6, IL-11, oncostatin M (OSM), and leukemia inhibitory factor (LIF), have gained recognition as factors that mediate crosstalk between stromal and immune cells, with diverse roles in numerous inflammatory and homeostatic processes. This review summarizes our current understanding of how IL-6 family cytokines control stromal-immune crosstalk in health and disease, and how these interactions can be leveraged for clinical benefit.