Despite major advances in redesigning and producing proteins through recombinant DNA technology, many therapeutic proteins are still produced by extraction from biological tissues or fluids, or from nonrecombinant microorganisms. Modification of such proteins, to improve potency and bioavailability and reduce immunogenicity, can only be carried out post-translationally by chemical-derivatization methods. Genetic- and chemical-modification methods are not mutually exclusive, however, and may be combined to optimize protein-engineering strategies, because chemical modification can introduce structural changes that are not encoded by DNA into both recombinant, and nonrecombinant proteins.