Cells are endowed with a rich surface coat of glycans that are carried as glycoproteins and glycolipids on the outer leaflets of their plasma membranes and constitute a major molecular interface between cells and their environment. Each cell's glycome, the sum of its diverse glycan structures, comprises a distinct cellular signature defined by expression levels of the enzymes responsible for glycan biosynthesis. This signature can be read by complementary glycan-binding proteins (GBPs) that translate glycan recognition into function. Nowhere is this more evident than in the immune system, where glycans and GBPs are integral to pathogen recognition and control of inflammatory responses. Glycobiology, the study of glycan structures and their functions, increasingly provides insight into immunoregulatory mechanisms and thereby provides opportunities for therapeutic intervention. This review briefly examines the makeup of the human glycome and the GBPs that translate glycan recognition into function and provides examples of glycan recognition events that are responsible for immune system regulation to promote wider appreciation of this rapidly expanding area of research.