Gangliosides make up a group of sialic acid-containing complex glycosphingolipids particularly abundant in the central nervous system. The finding indicating gangliosides are stored in certain hereditary diseases affecting the central nervous system opened the interest in studying their metabolism. The initial in vitro pioneering work on the glycosyltransferases involved in ganglioside biosynthesis was done by Roseman and his associates primarily in embryonic chick brains almost forty years ago. Since that time enzymes catalyzing the formation of main human gangliosides have been successfully purified and cloned. Their specificity has been determined and their subcellular localization and topology has been established. Transgenic mouse models deficient in distinct ganglioside-directed glycosyltransferases are available and represent a vital step toward understanding the metabolism and function of this challenging lipid class. In the present review we briefly introduce the reader in the complex structure of gangliosides, then we summarize new developments concerning their function especially regarding neurodegenerative disorders, and in this article we would like to review on what is known about glycosyltransferases that catalyze the formation of these complex lipids in the Golgi apparatus, that was established by Basu and his associates almost three decades ago.