New paradigms in cAMP signalling

► Molecular diversity of cAMP signalling molecules reviewed. ► Detection of cAMP with genetically engineered biosensors has provided a flurry of new information. ► cAMP synthesis may occur at intracellular sites by endocytosed receptor-G protein-adenylyl cyclase complexes. ► Preassembled receptor-G protein-adenylyl cyclase complexes are found intracellularly and may be clinically relevant. ► Hypothetical model of regenerative intracellular cAMP signal propagation is presented.