alpha-galactosidase (alpha-Gal) belongs to exoglycosidases, which distributed widely in the nature. alpha-Gal can be classified into two types: alpha-Gal A and alpha-Gal B. In vivo, alpha-Gal A is responsible for the cleavage of terminal alpha-galactosidic linkages in glycoconjungates; alpha-Gal B is an alpha-N-acetylgalactosaminidase in fact because it hydrolyses alpha-N-acetamidodeoxy-beta-D-galactosidic residues from the terminals of a variety of complex carbohydrates and glycoconjugates. Now progress is being made of these two isoenzymes, including studies on blood group conversion, xenotransplantation of organ and pathophysiology of lysosomal storage diseases. There will be significant improvement in the future clinical application of alpha-Gal.