A multistep series of adhesive and signaling events regulates inflammatory responses to infection or injury (1–3). To initiate these responses, circulating leukocytes must adhere to the vascular wall under shear forces. Selectins mediate the first adhesive step, which is characterized by tethering and rolling of leukocytes on endothelial cells, platelets, or other leukocytes (4, 5). L-selectin, expressed on most leukocytes, binds to ligands on some endothelial cells and on other leukocytes. E-selectin, expressed on cytokine-activated endothelial cells, binds to ligands on most leukocytes. P-selectin, expressed on activated platelets and endothelial cells, also binds to ligands on most leukocytes. The regulated expression of the selectins and their ligands helps initiate and terminate the inflammatory response. However, inappropriate expression of these molecules contributes to leukocyte-mediated tissue damage in a variety of inflammatory and thrombotic disorders (6). Each selectin is a type 1 membrane glycoprotein with an NH2-terminal C-type lectin domain, followed by an EGF-like domain, a series of short consensus repeats, a transmembrane domain, and a short cytoplasmic tail. Selectins mediate cell–cell adhesion through interactions of the lectin domains with specific glycoconjugate ligands. Like other mammalian lectins, the selectins bind selectively, but with low affinity, to particular oligosaccharides. All selectins bind to the tetrasaccharide sialyl Lewis x (sLex; 1 NeuAc 2, 3Gal 1, 4 [Fuc 1, 3] GlcNAc) and its isomer sialyl Lewis a (sLea; NeuAc 2, 3Gal 1, 3 [Fuc 1, 4] GlcNAc). L-and P-selectins, but not E-selectin, also bind to particular sulfated carbohydrates, such as heparan sulfate, that lack sialic acid and fucose (4, 5, 7). However, selectins bind with higher affinity or avidity to only a few glycoproteins. Most of these are mucins, ie, glycoproteins with multiple Ser/Thr-linked oligosaccharides (O-glycans) and repeating peptide motifs (4, 5). A key issue is whether any of these molecules mediates biologically relevant interactions with selectins (7). This perspective focuses on P-selectin glycoprotein ligand-1 (PSGL-1), a sialomucin with the most clearly defined function as a selectin ligand.