A large array of glycoproteins, glycolipids, and proteoglycans decorate the surfaces of animal cells. These glycoconjugates mediate many fundamental cellular processes, including cell-cell and cell-matrix adhesion, motility, growth, and signaling (28, 110). Over time, many pathogenic microorganisms have learned to exploit cell surface glycoconjugates as receptors for attachment, a process which ultimately facilitates tissue colonization and invasion. The interaction of specific proteins on the surface of microorganisms (adhesins) with carbohydrate chains on the glycoconjugate (receptors) enables the microbes to take their first step towards establishing an infection. This review concentrates on proteoglycans as adhesion receptors for bacteria, viruses, and parasites. Microbial binding to glycolipids and glycoproteins also occurs and has been discussed elsewhere (27, 40, 61–63, 85, 94). Proteoglycans are ubiquitous among animal cells, and as discussed below, their carbohydrate chains (glycosaminoglycans) bind many different protein ligands. Different experimental criteria have been used to establish a role for proteoglycans in attachment and invasion of host cells, including direct binding measurements, identification of microbial carbohydrate-binding proteins, competition studies with defined polysaccharides, loss of adhesion upon enzymatic removal of host glycans, and altered adherence to animal cell mutants with defective glycosaminoglycan biosynthesis. Overall, the experimental evidence for microbial adhesion to host cell proteoglycans is compelling, and future molecular studies may provide a basis for designing therapeutic strategies based on these interactions.