One hundred years have passed since Archibald Garrod postulated the one gene/one enzyme hypothesis. Since then, science has made significant progress and geneticists are now tackling an overwhelming complexity of gene regulation networks that underlie the genetics of complex human diseases. A particularly complex element in the biology of higher organisms is the genetics of protein glycosylation. Nearly all proteins that appeared after the emergence of multicellular life are glycosylated, but instead of being molded by a single gene, glycan structures are encoded within a network of several hundred glycosyltransferases, glycosidases, transporters, transcription factors and other proteins. In addition, in contrast to the linear structures of DNA and proteins, glycans have multiple branches that make their analysis significantly more challenging. However, recent developments in high throughput HPLC analysis have advanced glycan analysis significantly and it is now possible to address questions about the complex genetics of protein glycosylation. In this review we present some preliminary insights into this fascinating field.One hundred years have passed since Archibald Garrod postulated the one gene/one enzyme hypothesis. Since then, science has made significant progress and geneticists are now tackling an overwhelming complexity of gene regulation networks that underlie the genetics of complex human diseases. A particularly complex element in the biology of higher organisms is the genetics of protein glycosylation. Nearly all proteins that appeared after the emergence of multicellular life are glycosylated, but instead of being molded by a single gene, glycan structures are encoded within a network of several hundred glycosyltransferases, glycosidases, transporters, transcription factors and other proteins. In addition, in contrast to the linear structures of DNA and proteins, glycans have multiple branches that make their analysis significantly more challenging. However, recent developments in high throughput HPLC analysis have advanced glycan analysis significantly and it is now possible to address questions about the complex genetics of protein glycosylation. In this review we present some preliminary insights into this fascinating field.