Among all the systems developed by enterobacteria to face osmotic stress, only osmoregulated periplasmic glucans (OPGs) were found to be modulated during osmotic fluxes. First detected in 1973 by E.P. Kennedy’s group in a study of phospholipid turnover in Escherichia coli , OPGs have been shown across alpha, beta, and gamma subdivisions of the proteobacteria. Discovery of OPG-like compounds in the epsilon subdivision strongly suggested that the presence of periplasmic glucans is essential for almost all proteobacteria. This article offers an overview of the different classes of OPGs. Then, the biosynthesis of OPGs and their regulation in E. coli and other species are discussed. Finally, the biological role of OPGs is developed. Beyond structural function, OPGs are involved in pathogenicity, in particular, by playing a role in signal transduction pathways. Recently, OPG synthesis proteins have been suggested to control cell division and growth rate.