The receptor for the peptide hormone, cholecystokinin, is a G-protein-coupled receptor in the rhodopsin/beta-adrenergic receptor family. A number of methodological approaches have been utilized to gain insights into the molecular basis for natural peptide ligand binding and activation of this physiologically important receptor. Insights into this have come from sequence analysis, ligand and receptor structure-activity data, receptor mutagenesis, conformational analysis of ligand and receptor fragments, and photoaffinity labeling. In this work, we review the contributions of each of these complementary approaches and provide a current integrated view of the active complex of cholecystokinin bound to its receptor.