Glycosylation patterns in antibodies critically determine biological and physical properties but their precise control is a significant challenge in biology and biotechnology. We describe herein the optimization of an endoglycosidase‐catalyzed glycosylation of the best‐selling biotherapeutic Herceptin, an anti‐HER2 antibody. Precise MS analysis of the intact four‐chain Ab heteromultimer reveals nonspecific, non‐enzymatic reactions (glycation), which are not detected under standard denaturing conditions. This competing reaction, which has hitherto been underestimated as a source of side products, can now be minimized. Optimization allowed access to the purest natural form of Herceptin to date (≥90 %). Moreover, through the use of a small library of sugars containing non‐natural functional groups, Ab variants containing defined numbers of selectively addressable chemical tags (reaction handles at Sia C1) in specific positions (for attachment of cargo molecules or “glycorandomization”) were readily generated. You're the one that I want: The “blockbuster” antibody Herceptin was accessed with natural glycosylation through chemoenzymatic construction coupled with MS of the intact antibody (see picture). Herceptin was obtained with high purity (>90 %) when nonspecific, non‐enzymatic reactions (glycation) revealed by precise MS analysis were minimized. Glycosylation with unnatural sugars bearing tags also enabled the site‐selective attachment of cargo.