Recent advances in chemoselective ligation technology have made possible the modification of proteins with polymers in a site-specific and controlled manner. These approaches rely on the incorporation of chemoselective anchors into the protein backbone by either chemical or recombinant means, and subsequent modification with a polymer carrying a complementary linker. As a result, the assembly process and the covalent structure of the resulting protein-polymer conjugate are completely controlled, enabling the rational optimization of drug properties, in particular efficacy and pharmacokinetic properties. Application of chemoselective ligation technologies to cytokines and chemokines has led to the generation of new lead proteins for use as erythropoietic agents and HIV fusion inhibitors.