Therapeutic proteins can be pharmacologically improved by conjugative post-translational modifications (PTMs) through the rational design of their structure and production process. N- and O- linked glycosylation can confer advantages to proteins and can be controlled by the process conditions, producing cell line and enzymatic expression or activity. The resulting glyosidic profile influences their pharmacological features such as in velaglucerase alfa. Conjugation of polyethylene glycol (PEG) onto therapeutic proteins has been used to overcome pharmacological limitations. They can be site-specifically or randomly linked through the reaction between a terminal group of PEG and an amino acid residue group of the protein. Both protein and PEG components participate in pharmacological mechanisms, enabling a longer half-life for peginterferon beta-1a, for example. Fatty acylation of proteins occurs in cells via some known reactions that may involve different linkages, fatty acids, modified residues, and enzymes. Insulin degludec is a fatty acylated biopharmaceutical formulated to solve the problem of variability in insulin exposure associated with other products. Other potential uses of conjugative PTMs for pharmacological improvement of therapeutic proteins are proposed in this paper.