Galectin-3-binding protein (Gal-3BP) is a ubiquitous and multifunctional secreted glycoprotein originally identified and mainly studied in the context of neoplastic transformation and cancer progression. However, Gal-3BP expression is induced in viral infection and by a multitude of molecules that either mimic or are characteristic for an ongoing inflammation and microbial infection, such as IFN-α, IFN-β, IFN-γ, TNF-α, poly(I:C), dsRNA, and dsDNA. Furthermore, Gal-3BP belongs to the scavenger receptor cysteine-rich (SRCR) domain-containing protein family, by virtue of its N-terminal SRCR domain. The SRCR domain is found in soluble or membrane-associated innate immunity-related proteins and is implicated in self-nonself discrimination. This review summarizes the current knowledge of structural features of Gal-3BP and its proposed intracellular and extracellular innate immunity functions with special emphasis on viral and bacterial infections.