Signalling via the large family of G protein-coupled receptors (GPCRs) can lead to many cellular responses, ranging from regulation of intracellular levels of cAMP to stimulation of gene transcription. Members of this receptor family have been grouped into different categories dependent on the particular G protein subtypes that they predominantly interact with. Thus, receptors that couple to GS proteins will stimulate adenylate cyclase in many cells, while Gq/11-coupled receptors can mobilize intracellular Ca2+ via activation of phospholipase C. There is accumulating evidence, however, that activation of one particular signalling pathway by a GPCR can amplify intracellular signalling within a parallel but separate pathway. In this article Lisa Selbie and Stephen Hill review some of the evidence for these synergistic interactions and suggest that they may have an important role in finetuning signals from multiple receptor signalling pathways.