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It is well established that glucans enhance the efficacy of anti-cancer and anti-infection immunotheraphy, both in clinical and experimental conditions. However, the considerable variations among batches of natural glucan in molecular weight, branching frequency, as well as linkage to chitins and mannoproteins, make the clinical applications of natural glucan questionable. The future might be in the use of small synthetic oligosaccharides prepared on the basis of natural glucans. Some of these non natural oligosaccharides showed biological activities such as stimulation of phagocytosis, modulation of gene expression and anti-cancer activity, which were superior to natural glucans. The recent studies strongly suggest the possibility of small chemical changes in the structure of these oligoglucans oriented towards their improved biological activities. This review highlights recent achievements in the immunological effects of synthetic, glucan-based oligosaccharides.