Infection by pathogens is generally initiated by the specific recognition of host epithelia surfaces and subsequent adhesion is essential for invasion. In their infection strategy, microorganisms often use sugar-binding proteins, that is lectins and adhesins, to recognize and bind to host glycoconjugates where sialylated and fucosylated oligosaccharides are the major targets. The lectin/glycoconjugate interactions are characterized by their high specificity and most of the time by multivalency to generate higher affinity of binding. Recent crystal structures of viral, bacterial, and parasite receptors in complex with human histo-blood group epitopes or sialylated derivatives reveal new folds and novel sugar-binding modes. They illustrate the tight specificity between tissue glycosylation and lectins.