G-protein coupled receptors (GPCRs) represent the single largest class of druggable targets in the human genome. Of the 390 or so druggable and non-olfactory human GPCRs there exist many which are orphan and/or understudied; we refer to these as "oGPCRs". In this talk I will show how new technologies developed by my lab can illuminate the pharmacology, signaling pathways, chemical biology, distribution and function of GPCrs. I will highlight our new open-source tools which include open-access repositories of chemical probe molecules, reporter plasmids and engineered animals that enable investigators to interrogate the biological functions of GPCRs. Given the central importance of GPCRs for all areas of biomedical research, illuminating the pharmacology, function, signaling and chemical biology of known GPCRs and oGPCRs will have far-reaching impact for both therapeutics and basic biomedical science.