Cations bind to the pi face of an aromatic structure through a surprisingly strong, non-covalent force termed the cation-pi interaction. The magnitude and generality of the effect have been established by gas-phase measurements and by studies of model receptors in aqueous media. To first order, the interaction can be considered an electrostatic attraction between a positive charge and the quadrupole moment of the aromatic. A great deal of direct and circumstantial evidence indicates that cation-pi interactions are important in a variety of proteins that bind cationic ligands or substrates. In this context, the amino acids phenylalanine (Phe), tyrosine (Tyr), and tryptophan (Trp) can be viewed as polar, yet hydrophobic, residues.