Cardiac myocytes respond to biomechanical stress by initiating cellular processes that lead to hypertrophy. Although cardiac hypertrophy is a response to increased stress on the heart, it is also associated with elevated plasma catecholamine levels and an increase in cardiac morbidity and mortality. Understanding the cellular signals that initiate the hypertrophic response is of critical importance in identifying pathways that mediate the hypertrophic heart's maladaptive deterioration to cardiac failure. Here we present data demonstrating an important role for G protein-coupled receptors in the induction of in vivo cardiac hypertrophy and the activation of signaling pathways, such as the mitogen activated protein kinase and phosphoinositide-3 kinase pathways.