Progress in determining crystal structures of G protein-coupled receptors (GPCRs) has rapidly increased our knowledge of structural aspects governing GPCR signallingâ greatly enhancing our understanding of relevant non-structural work as well. Thorough examination of current structural information yields important insights as to the function of these receptors. Through our in-depth analysis of rhodopsin in a variety of photointermediate states, it is possible to understand some of the roles which conserved motifs, including ordered water molecules, play in the activation of rhodopsin and, by extension, other GPCRs. Many aspects of the GPCR activation process remain unresolved; only through high resolution determination of agonist-bound and G protein-bound GPCR structures will we be able to discern those critical structural determinants in GPCRs that couple the binding of ligand to G protein activation and concomitant nucleotide exchange.