Investigating the intricate mechanisms of G protein-coupled receptor (GPCR) signalling in living cells is far from trivial. Over the last 20 years, the rise of genetically encoded resonance energy transfer (RET) sensors has shed new light onto the mechanisms of GPCR signalling. Such findings have challenged classical views on GPCR signalling and enhanced our understanding of the spatiotemporal dimensions of GPCR activity, leading to the discovery of endosomal GPCR signalling. This review highlights the use of RET sensors to monitor GPCR signalling in real-time and in live cells, focusing on GPCR activation and trafficking, and second messenger activity. It explores the physiological relevance of illustrative cases of endosomal signalling and discusses potential avenues to improve RET approaches to further explore endogenous GPCR activity in physiologically relevant contexts.