Galectins regulate a wide variety of biological processes. However, one of the earliest and most common galectin activities is likely their ability to recognize microbes. Galectin binding to microbes can result in direct microbial killing and activation of host immunity, eventually enhancing the ability of a host to eliminate microbes. However, microbes appear to have also evolved the ability to utilize galectins to enhance host attachment, ultimately leading to increased risk for infection. The ability of galectins to directly engage microbes, coupled with their role in regulating host immune function, positions these carbohydrate binding proteins as key factors that can dictate the consequence of microbial exposure. In this way, galectins represent a highly pleiotropic protein family involved in the regulation of a broad range of host-microbial interactions.