Intramolecular and intermolecular communication is a privileged issue in G protein-Coupled Receptor (GPCR) function as the prominent role of these receptors is to respond to extracellular signals by catalyzing nucleotide exchange in intracellular G proteins. In the last decade or so we have applied much effort in elaborating computational strategies to infer the mechanisms of intramolecular and intermolecular communication in a number of GPCRs of the rhodopsin family. In this article, we review the most relevant achievements on the matter. In summary, the receptor sites of activating mutations or ligand-binding communicate with a common allosteric site in the cytosolic domains. This was inferred from the observation that local perturbations by activating mutations or ligands correlate with increases in solvent accessibility of the neighborhoods of the highly conserved E/DRY receptor motif. The latter turned out to be the primary recognition point for the C-terminus of the G protein α-subunit, independent of the receptor or the G protein type. In spite of the highly composite nature of the receptor-G protein interface, receptor contacts with the C-terminus of the α5-helix seem to be the major players in the receptor-catalyzed formation of a nucleotide exit route. The latter would lie in between the αF-helix and the β6/α5 loop, which detach from each other upon receptor binding, giving solvent accessibility to the nucleotide. A worthy inference of the studies is that GPCRs employ common pathways for the transfer of functionally relevant information.