Therapeutic monoclonal antibodies (mAbs) are mostly of the IgG class and constitute highly efficacious biopharmaceuticals for a wide range of clinical indications. Full-length IgG mAbs are large proteins that are subject to multiple posttranslational modifications (PTMs) during biosynthesis, purification, or storage, resulting in micro-heterogeneity. The production of recombinant mAbs in nonhuman cell lines may result in loss of structural fidelity and the generation of variants having altered stability, biological activities, and/or immunogenic potential. Additionally, even fully human therapeutic mAbs are of unique specificity, by design, and, consequently, of unique structure; therefore, structural elements may be recognized as non-self by individuals within an outbred human population to provoke an anti-therapeutic/anti-drug antibody (ATA/ADA) response. Consequently, regulatory authorities require that the structure of a potential mAb drug product is comprehensively characterized employing state-of-the-art orthogonal analytical technologies; the PTM profile may define a set of critical quality attributes (CQAs) for the drug product that must be maintained, employing quality by design parameters, throughout the lifetime of the drug. Glycosylation of IgG-Fc, at Asn297 on each heavy chain, is an established CQA since its presence and fine structure can have a profound impact on efficacy and safety. The glycoform profile of serum-derived IgG is highly heterogeneous while mAbs produced in mammalian cells in vitro is less heterogeneous and can be "orchestrated" depending on the cell line employed and the culture conditions adopted. Thus, the gross structure and PTM profile of a given mAb, established for the drug substance gaining regulatory approval, have to be maintained for the lifespan of the drug. This review outlines our current understanding of common PTMs detected in mAbs and endogenous IgG and the relationship between a variant's structural attribute and its impact on clinical performance.