Since the approval of insulin in 1982 as the first recombinant protein, an impressive development has taken place. Meanwhile, more than 120 of recombinant drug substances have been approved and become available as extremely valuable therapeutic options. Based on a somewhat artificial but useful system one can classify recombinant drugs as first generation (changes due to technological concessions), second generation (authentic biomolecules), third generation (deliberately introduced modifications in order to improve mainly pharmacokinetic properties) and fourth generation drugs (newly invented, artificial proteins). Authenticity – exact copying of the most common human form – is not anymore a value per se, as challenges primarily related to the pharmacokinetics of artificial recombinant drugs can be overcome by diverging from the original. On the other hand, relatively minor changes in manufacturing or packaging may impact safety of therapeutic proteins.