The development of new therapeutic drugs acting at G protein-coupled receptors (GPCRs) whose ligand specificity is known is of great importance to the pharmaceutical industry and to the population at large. It is also vital that surrogate ligands can be identified for GPCRs at which the endogenous ligand(s) remain unknown so that their potential as drug targets can be assessed. It is against this background that we consider a selection of technologies that are emerging to meet these challenges.