G protein-coupled receptor (GPCR) signalling pathways underlie numerous physiological processes, are implicated in many diseases and are major targets for therapeutics. There are more than 800 GPCRs, which together transduce a vast array of extracellular stimuli into a variety of intracellular signals via heterotrimeric G protein activation and multiple downstream effectors. A key challenge in cell biology research and the pharmaceutical industry is developing tools that enable the quantitative investigation of GPCR signalling pathways to gain mechanistic insights into the varied cellular functions and pharmacology of GPCRs. Recent progress in this area has been rapid and extensive. In this Review, we provide a critical overview of these new, state-of-the-art approaches to investigate GPCR signalling pathways. These include novel sensors, Förster or bioluminescence resonance energy transfer assays, libraries of tagged G proteins and transcriptional reporters. These approaches enable improved quantitative studies of different stages of GPCR signalling, including GPCR activation, G protein activation, second messenger (cAMP and Ca2+) signalling, β-arrestin recruitment and the internalisation and intracellular trafficking of GPCRs.