Biochemical studies have revealed the propensity of aromatic amino acid residues to mediate important contacts in complexes involving proteins and peptides. This phenomenon is explained by the unique properties of aromatic groups, which enable several types of intermolecular interactions and extensive binding interfaces. Protein receptors recognize aromatic residues within deep binding pockets or at large hydrophobic surfaces, but the smaller size of synthetic receptors typically limits their interactions to a single residue. Therefore, synthetic receptors need efficient ligands, and aromatic groups meet this need. Proteins often present multiple aromatic sites on their surface, however, and thus it can be challenging to target a single site. This limitation can be overcome by targeting the terminal residue, which presents a small, unique, and solvent-accessible epitope, as demonstrated in particular with cucurbit[n]uril recognition of N-terminal aromatic residues. Moreover, protein termini are also less mechanically constrained than other positions in the polypeptide chain. Termini can unfold and become solvent exposed in order to accommodate receptor binding in both natural and designed systems. The combination of an aromatic side chain, the terminal ammonium group, and the flexibility of the chain terminus has enabled predictive recognition of proteins on the basis of the amino acid sequence.