G protein-coupled receptors (GPCRs) are the cornerstone of intercellular communication throughout the human body, where they control diverse physiological functions such as blood pressure, neural activity and reproduction. GPCRs have also been implicated in the pathogenesis of cancer, inflammatory diseases, metabolic imbalances and neurological disorders, and are therefore the targets of over 30% of marketed small-molecule drugs. Integral membrane proteins such as GPCRs are challenging targets for structure determination. However, generic methodologies developed over the last decade have revolutionized the field with over 20 unique GPCR structures determined, and some co-crystallized with over ten different ligands. Structure-based drug design for GPCRs is now a reality and has the potential to accelerate the development of novel therapeutics for the treatment of a wide range of disorders and diseases.