The number of glycan determinants that comprise the human glycome is not known. This uncertainty arises from limited knowledge of the total number of distinct glycans and glycan structures in the human glycome, as well as limited information about the glycan determinants recognized by glycan-binding proteins (GBPs), which include lectins, receptors, toxins, microbial adhesins, antibodies, and enzymes. Available evidence indicates that GBP binding sites may accommodate glycan determinants made up of 2 to 6 linear monosaccharides, together with their potential side chains containing other sugars and modifications, such as sulfation, phosphorylation, and acetylation. Glycosaminoglycans, including heparin and heparan sulfate, comprise repeating disaccharide motifs, where a linear sequence of 5 to 6 monosaccharides may be required for recognition. Based on our current knowledge of the composition of the glycome and the size of GBP binding sites, glycoproteins and glycolipids may contain ∼3000 glycan determinants with an additional ∼4000 theoretical pentasaccharide sequences in glycosaminoglycans. These numbers provide an achievable target for new chemical and/or enzymatic syntheses, and raise new challenges for defining the total glycome and the determinants recognized by GBPs.