residues, with a long tail extending towards larger proteins like lysozyme and lactoferrin . AMPs are typically cationic and hydrophobic, with a net positive charge around +3e o and a hydrophobic residue content of approximately 50%. The diverse chemical space of AMPs reflects the variety of organisms that produce them -ranging from mammals and insects to plants, amphibians, and microorganisms -as well as the wide heterogeneity of bacterial species and strains they target. AMPs are part of the innate immune response in many organisms or may serve as a competitive mechanism in microbial ecosystems . This review aims to identify and predict trends in AMP discovery by examining both historical and contemporary approaches. The discovery of AMPs dates back to 1922 when Sir Alexander Fleming serendipitously identified lysozyme and its antimicrobial activity. Early AMP discoveries, such as Colistin, Daptomycin, and Gramicidin, came from painstaking isolation efforts from soil samples . However, the clinical development of AMPs has been marked by alternating periods of success and challenge, often due to the balance between efficacy and side effects , caused by the peptides' suboptimal pharmacokinetic (PK) properties . The technological limitations of early peptide synthesis, combined with a lack of understanding of key concepts such as structure-toxicity relationships (STR), structure-activity relationships (SAR), and PK, further hindered their development. As a result, from the 1960s to 2000, peptide therapeutics, including AMPs, as a whole were still underrepresented in the clinic. AMPs were largely overshadowed by small-molecule antibiotics, which were cheaper and more easily administered orally.