A consideration of improbable structures in nature and the link between improbable and novel structures. Creation of molecules by synthesis and by using biological systems. The history of beta lactams as improbable structures and their eventual resolution. Hermeneutics and natural products. The example of glucosinolates as a misassigned structure and the eventual unveiling of the correct structure by synthesis and X-ray crystallography. The development of combinatorial chemistry and natural product libraries. Beta lactams and beta lactamases in the study of adaptive responses. Anti-microbial resistance (AMR) and its inevitability. The concept of quorum sensing and its use as a tool to overcome AMR. The complexity of microbiomes and cell–cell communication.