Cardiac myocytes have signaling pathways that agonize and antagonize hypertrophic growth. Neuroendocrine factors typically stimulate G protein–coupled receptors (GPCRs) and/or receptor tyrosine kinases (RTKs), which activate an array of intermediate signaling factors that ultimately drive the hypertrophic response. RTKs are typically coupled to adaptor and exchange factors such as Grb2 and SOS that induce Ras activation, or to Src kinase family members. GPCRs are typically coupled to G proteins that induce a number of signaling events such as phospholipase C (PLC) activation. Alternatively, cardiac myocytes may also directly respond to alterations in loading or stretching through internal sensors that link to prohypertrophic signal transduction cascades. In contrast, the action of ANP and BNP through the atrial natriuretic peptide receptor GC-A stimulates the production of cGMP and PKG, which function to antagonize hypertrophic growth within the cardiac myocyte itself. KHD, kinase-homology regulatory domain; GC, guanylyl cyclase catalytic domain.