The noncovalent interaction between medicinal chemistry-relevant heterocycles and protein amide groups was studied in detail in the Full Paper by Michael Harder, Bernd Kuhn, and Francois Diederich (p. 397 ff.). The front cover picture shows two examples of protein binding sites that expose backbone amides for ligand interaction: in the background, the extended beta sheet structure of an amyloid is shown, and in the top-right, the solvent-accessible surface of the active site of cathepsin L is displayed. The base of the S3 pocket, which is formed by a glycine-containing dipeptide fragment of the cathepsin L backbone, is highlighted. To optimally exploit the interaction with such motifs in ligand design, guidelines are devised based on extensive quantum chemical calculations on various arene/amide dimers. Both a correlation of the interaction strength with the magnitude of the fragment dipole moment and a significant energetic preference for an antiparallel alignment of the interacting dipole vectors could be demonstrated.