G protein-coupled receptors (GPCRs) mediate cellular responses to a diverse array of extracellular messenger molecules. Recent studies have shown that GPCR-mediated signaling pathways include transactivation of receptor tyrosine kinases (RTKs), such as receptors for epidermal growth factor, platelet-derived growth factor, neurotrophins and fibroblast growth factor. Cross-communication between GPCRs and RTKs is a complex process, and utilizes sets of signaling molecules that are primarily determined by cell context and the types of receptors activated. The differential involvement of RTKs and downstream signaling pathways activated in response to GPCR-mediated stimulation elicits a variety of cellular effects during development, proliferation, differentiation, survival, repair and synaptic transmission in the CNS.