In recent years, an important role has emerged for the glycan‐binding protein Galectin‐9 (Gal‐9) in health and disease. In normal physiology, Gal‐9 seems to be a pivotal modulator of T‐cell immunity by inducing apoptosis in specific T‐cell subpopulations. Because these T‐cell populations are associated with autoimmunity, inflammatory disease, and graft rejection, it was postulated that application of exogenous Gal‐9 may limit pathogenic T‐cell activity. Indeed, treatment with recombinant Gal‐9 ameliorates disease activity in various preclinical models of autoimmunity and allograft graft rejection. In many solid cancers, the loss of Gal‐9 expression is closely associated with metastatic progression. In line with this observation, treatment with recombinant Gal‐9 prevents metastatic spread in various preclinical cancer models. In addition, various hematological malignancies are sensitive to apoptotic elimination by recombinant Gal‐9. Here, we review the biology and physiological role of this versatile lectin and discuss the therapeutic potential of Gal‐9 in various diseases, including autoimmunity, asthma, infection, and cancer.