Despite their recognized importance for therapeutic proteins, the production of structurally defined glycans is still a challenging issue. However, an increased understanding of glycosylation pathways, recent advances in analytical tools, and emerging technologies for subcellular targeting using chimeric glycosyltransferases are facilitating the rational design of new glycan biosynthetic pathways. Plants are particularly amenable to glyco-engineering approaches and thus they are increasingly being used for the production of recombinant proteins. Here we summarize the main achievements in the field of in planta glyco-engineering for the production of therapeutically relevant proteins.