Many G-protein-coupled receptors regulate cellular functions by coupling to G-proteins of the G_q/G₁₁ and G₁₂/G₁₃ family. In recent years we have generated mouse mutants in which the genes coding for the a-subunits of these proteins have been inactivated constitutively as well as conditionally. This has opened the possibility to systematically analyze the role of G_q/G₁₁- as well as G₁₂/G₁₃-mediated signalling pathways in physiological and pathophysiological processes like platelet activation in hemostasis and thrombosis, myocardial hypertrophy, angiogenesis or various functions of the nervous system. Recent projects will be presented which illustrate the role individual G-protein mediated cellular signalling pathways play on a supra-cellular level.