Bifunctional chemical tools containing a covalent warhead and a bio-orthogonal moiety have an almost limitless utility and scope for interrogating biological processes. The development of such bifunctional chemical tools to study G protein-coupled receptors (GPCRs) will be presented. The adenosine A1 receptor (A1R) is a GPCR that plays an important role in human pathophysiology. As such, we are developing bifunctional chemical tools to better understand A1AR signalling and regulation. We designed and synthesised a series of xanthine-bicyclo[2.2.2]octane-derived A1R ligands that can firstly covalently bind to A1R (sulfonyl fluoride reacts with tyrosine) and secondly be ‘clicked’ (copper-catalysed azide-alkyne cycloaddition) to a marker or tag. This two-step approach allows for versatility in fluorophore/probe and is amenable to rigorous washing. The design, synthesis and structure-activity-relationships of this compound series will be presented, along with receptor labelling studies. We are now developing ‘second-generation’ bifunctional tools for A1R with different warheads, and/or based on different ligand scaffolds, in addition to developing new ‘click’ chemistry approaches that do not require a metal catalyst. In another project, bifunctional chemical tools for the cannabinoid type 2 receptor ligand are being developed.