The G-protein-mediated signalling system has evolved as one of the most widely used transmembrane signalling mechanisms in mammalian organisms. All mammalian cells express G-protein-coupled receptors as well as several types of heterotrimeric G-proteins and effectors. G-protein-mediated signalling is involved in many physiological and pathological processes. This review summarizes some general aspects of G-protein-mediated signalling and focusses on recent data especially from studies in mutant mice which have elucidated some of the cellular and biological functions of heterotrimeric G-prtoteins.