The stabilization energies of Glu-Lys salt bridges are calculated at the CCSD(T) complete basis set limit to provide a reasonable description of the strength of the ion-pair bond in the gas phase. The effect of the environment (protein with ε = 4 and water with ε = 80) on the stabilization energy was introduced via a modification of the quantum chemical DFT energy, for which the COSMO methodology was adopted. The other (standard) approach was based on incorporating a dielectric constant into the Coulomb electrostatic term of the Amber empirical potential function and utilizing the generalized Born model implemented in the Amber program. The environment affects the stabilization energy of the salt bridge dramatically: The protein reduces the energy to less than one half of the original value, whereas water sometimes changes stabilization to destabilization. Both theoretical procedures, based on completely different theoretical backgrounds, yield very similar results, which strongly support their validity. An ion pair is converted to an ion-neutral pair when its pH is changed. This transformation is connected with a strong reduction of the stabilization energy regardless of the environment. The substantial differences in the stabilization energies of ion pairs and ion-neutral pairs contradict the negligible changes of free energy detected experimentally. Evidently, the contribution of formation and hydration entropy is significant and compensates for the large stabilization energies.