Oligosaccharidoses are rare genetic disorders caused by mutations of genes that code for lysosomal enzymes that catalyse the degradation of oligosaccharides. In addition, this chapter describes a variety of hereditary metabolic disorders such as defects in glycoprotein degradation that present with signs and symptoms similar to the oligosaccharidoses. Oligosaccharides are short-chain polymers of simple sugars that are attached to polypeptides to form glycoproteins, which are important connective tissue constituents binding cells. Thus, they are integral parts of cell membranes and functional glycoproteins including antibodies. Oligosaccharidoses were identified after mucopolysaccharidoses had been delineated, and they share similar physical and pathologic features. The best described disorders are GM1Gangliosidosis, α-and β-Mannosidosis, Fucosidosis, and Sialidosis. The physical appearance of these patients may closely resemble those of mucopolysaccharidoses, especially their coarse facial features. Radiographs may show mild dysostosis multiplex. Abnormal vacuoles are seen in peripheral lymphocytes. Diagnoses are confirmed with biochemical and molecular studies described in this chapter. Determination of partially degraded urinary oligosaccharides by mass spectrometry is a major diagnostic tool in patients with a suspected oligosaccharidosis The prognosis for most patients with oligosaccharidoses is currently dismal because very little is available for treatment other than supportive care.