Glycans play a crucial role to discern between self and foreign entities by providing key recognition elements for C-type lectin receptors (CLRs) and Siglec receptors expressed on immune cells. The glycan recognition of CLRs has illustrated a potent immune modulatory role affecting not only innate pathogen binding and immune signalling, but also Thelper differentiation, cytokine production and antigen presentation. This broad range of influence has implicated glycans in the pathogenesis of infectious diseases but also revealed their extraordinary properties in cancer. Glycan binding by CLRs and Siglecs can be exploited for immunotherapy and the design of glycan-based therapeutics and their multivalent requirements will aspire new biotechnological approaches to effectively interfere in immunological processes in cancer and infectious diseases.