A large body of evidence indicates that agonists of some G protein-coupled receptors (GPCRs) can activate growth factor receptor tyrosine kinases (RTKs) in the absence of added growth factor. This phenomenon, called transactivation, is an important pathway that contributes to growth-promoting activity of many GPCR ligands. Reciprocally, recent advances indicate that RTKs utilize GPCR signalling molecules to transduce signals and that RTK ligands themselves can transactivate GPCRs. This novel transactivation process, which places GPCR signalling downstream of RTKs, either requires the production of a GPCR ligand of the transactivated GPCR or occurs in a ligand independent manner within an integrated signalling network. Here, we provide an overview of the molecular mechanisms involved in this novel cross-communication between GPCRs and RTKs and discuss its relevance in the specification of growth factor signalling and functions.