Lectins are multifunctional carbohydrate-binding proteins that can recognize various carbohydrates on cell surfaces and extracellular matrix, and are involved in several biological processes. Galectins, a family of animal lectins with affinity for β-galactoside-containing oligosaccharides, are expressed by several cells of the immune system and tissue-resident stromal cells. Increasingly, experimental evidence indicates that galectins might play critical regulatory roles in cancer, fibrosis and chronic inflammatory disorders, such as rheumatoid arthritis. In this review, we summarize recent developments in our understanding of the galectins’ roles within particular cells, and in the broader context of the inflammatory or tumor microenvironments. This body of knowledge, documenting the coming-of-age of galectins as potential immunosuppressive agents or targets for anti-inflammatory drugs, represents a sound basis to further explore their immunoregulatory properties in the development of novel therapies for autoimmune diseases and chronic inflammation.