This chapter focuses the consequences of structural heterogeneities for human IgG antibodies, with some appropriate diversions. Residues within light and heavy chain complementarity determining regions (CDRs) susceptible to posttranslational (PTM) and chemical modifications (CMs) have been shown to compromise binding activity. However, currently available techniques allow for sequence analysis at the clone selection stage, such that molecules with CDR residues susceptible to modification can be. Unique N-terminal sequence may be obtained for the heavy and light chains of most monoclonal IgG paraproteins; for others, however, the N-terminal amino acid yield may not be quantitative or appear to be entirely "blocked". Methionine residues within variable region framework sequences regions have not been reported to be vulnerable to oxidation, owing to the compact domain structure, while residues exposed within CDRs may be. Innovative studies have explored engineering of the protein moiety to selectively enhance biologic activities; however, these are mutant forms of IgG, that is, nonself, that may enhance immunogenicity.