G protein-coupled receptors (GPCRs) are the largest superfamily of cell surface receptor proteins and a major target class for drug development. GPCRs are inherently flexible proteins that have evolved to allosterically communicate external signals to modulation of cellular function through recruitment and activation of transducer proteins, particularly G proteins. Technological evolution in cryo-EM combined with continuing advances in biochemical approaches for the stabilisation of active-state complexes of GPCRs with different transducer proteins is now enabling structural interrogation of receptor activation and transducer engagement. This has opened up unparalleled insight into GPCR structure and molecular details of peptide and small molecule binding that is facilitating mechanistic understanding of ligands of distinct pharmacology, including differential efficacy and allosteric modulation. Using the glucagon-like peptide-1 receptor (GLP-1R) as an exemplar, I will illustrate how we are using cryo-EM to understand ligand pharmacology and will then discuss the current and future application of cryo-EM to GPCR drug discovery and development.