Spectral tuning by visual pigments involves modulation of physical properties of the 11-cis-retinylidene protonated Schiff base (PSB) chromophore by amino acid side chains in and around the chromophore-binding pocket. Specific molecular contacts between the chromophore and the amino acid side chains of the opsin chromophore-binding pocket have been determined recently using an interdisciplinary approach consisting of site-directed mutagenesis, optical and vibrational spectroscopy, and molecular graphics modelling. These studies provide insight into the mechanism of spectral tuning among visual pigments. In blue pigments a majority of the opsin shift is caused by polar amino acid side chains arrayed about the PSB to increase the energy gap between the ground (S0) and excited states (S1). In addition, a specific tyrosine near the chromophore ring causes a decrease in solvent polarizability. Other amino acid residues alter the binding pocket structure to strengthen electrostatic interaction between the PSB and its counterion and/or solvent dipoles. In the green and red pigments, the work of Kochendoerfer et al (1997; Biochemistry 26:6577-6587) demonstrates that local structural perturbations at the PSB or elsewhere are not responsible for spectral tuning. Instead, the green-to-red opsin shift is best explained by dipolar side chains near the chromophore ring that lower the transition energy that occurs upon electronic excitation by affecting the change in electric dipole moment. In summary, the absorption maximum of a visual pigment is primarily regulated by the interaction of the chromophore charge distribution with dipolar residues in its opsin chromophore-binding pocket. The work presented in this paper is reported in greater detail in Lin et al.