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G protein-coupled receptors or GPCR are the most abundant membrane receptors in our genome with around 800 members. They play an essential role in most physiological and pathophysiological phenomena. In addition, they constitute 30% of the targets of currently marketed drugs and remain an important reservoir for new innovative therapies. Their main effectors are heterotrimeric G proteins. These are composed of 3 subunits, α, β and γ, which, upon coupling with a GPCR, dissociate into G α and G βγ to activate numerous signaling pathways. This article describes some of the recent advances in understanding the function and role of heterotrimeric G proteins. After a short introduction to GPCRs, the history of the discovery of G proteins is briefly described. Then, the fundamental mechanisms of activation, signaling and regulation of G proteins are reviewed. New paradigms concerning intracellular signaling, specific recognition of G proteins by GPCRs as well as biased signaling are also discussed., (© Société de Biologie, 2022.)