While ribosomal antimicrobial peptides were mainly considered in the past to be linear, containing a few to several cationic amino acids, often showing membrane-interacting and poreforming activity, the identification of several new classes of RiPPs in the past 15 years has changed this dogma. Today, several highly complex RiPPs are known, which are so heavily post-translationally modified including via additional ring systems, epimerizations, hydroxylations, acylations, and/or C-and N-methylations that they can hardly be recognized as being of ribosomal biosynthesis origin. However, the big difference to NRPS-derived peptides is that RiPPs initially rely only on the 20 canonical amino acids while in NRPS-derived peptides more than 400 different amino acids have been described. While most of these are incorporated into the peptide during the assembly-line-like mechanism, where they can also be modified including by C-and N-methylation, hydroxylation, oxidation, dehydration, heterocyclization, acylation, or formylation. The resulting peptide can also be further modified post-NRPS by glycosylation, phosphorylation, sulfation, or deacylation. Furthermore, NRPS can occur in combination with polyketide synthases (PKS), forming so-called NRPS-PKS hybrid enzymes, based on the shared biochemical mechanism, whereby all biosynthesis intermediates are covalently bound to a peptidyl-or acyl-carrier protein or thiolation (T) domain, ensuring an efficient combination of amino acids with (further functionalized) malonyl-or acetyl-units. The resulting gamma-(elongation with one) or epsilon-(elongation with two PKS units) amino acids can add to the complexity of NRPS-derived peptides beyond what is possible through RiPPs.