Our understanding of signal transduction via G-protein-coupled receptors (GPCR) has developed dramatically during the last decades. The initial idea of linear signalling pathways transferring information from the cell membrane to the nucleus has evolved into a complicated network of signalling pathways offering the possibility of crosstalk, fine tuning and specific regulation at multiple levels. During the recent meeting on GPCRs at the Karolinska Institutet, Stockholm novel aspects of GPCR signalling were presented and discussed. Here, we will discuss several possibilities for GPCRs to achieve specificity in signal transduction, such as the phenomenon of biased agonism, receptor multimerization, the role of co-receptors, the regulation of heterotrimeric G proteins as well as multiple G(s)-dependent pathways to extracellular single-regulated protein kinases.