Cell surface complex carbohydrates have emerged as key recognition molecules, mediating physiological interactions between cells. Typically, glycans on one cell surface are engaged by complementary carbohydrate binding proteins (lectins) on an apposing cell, initiating appropriate cellular responses. Although many cell surface lectins have been identified in vertebrates, only a few of their endogenous carbohydrate ligands have been established. Each major class of cell surface glycans-glycoproteins, glycolipids, and proteoglycans-has been implicated as physiologically relevant lectin ligands. The current minireview focuses on findings that implicate glycosphingolipids as especially important molecules in cell-cell recognition in two different systems: the recognition of human leukocytes by E-selectin on the vascular endothelium during inflammation and the recognition of nerve cell axons by myelin-associated glycoprotein in myelin-axon stabilization and the regulation of axon regeneration.