Hexofuranosides are widely spread in nature, and notably in numerous pathogenic microorganisms. This particular five-membered ring for hexosides leads to novel biological properties and, as usual in glycochemistry, to completely different reactivity and selectivity. Far from being exhaustive, this review will first focus on the structure of the oligosaccharidic part of hexofuranosyl conjugates found in natural sources. Original syntheses will then be presented, stressing more particularly on the development of chemical and chemo-enzymatic tools for the access to 1,2-trans or 1,2-cis linkages. Finally, innovative applications related to biological, chemical and physicochemical fields for both natural and synthetic hexofuranosyl compounds will be described.