The natriuretic peptide comprises at least three ligands(ANP, BNP, and CNP) and three receptors(GC-A, GC-B, and Clearance receptor). ANP and BNP are cardiac hormones, which regulate blood pressure and body fluid volume. Angiotensin II, the effector peptide of the renin-angiotensin system, regulates cellular growth in response to developmental, physiological and pathological processes. Recently, evidences suggest that cardiovascular homeostasis is determined by the balance between these two important counter-regulatory pathways. In this paper, we will discuss the molecular mechanism of the cross-talk between the two systems, including our recent findings using the mice deficient for GC-A and angiotensin II receptors. The results suggest that the endogenous natriuretic peptide system inhibits the cardiac angiotensin system and protects the heart from excessive pathological remodelings.