A growing body of evidence indicates that activation of angiotensin II (Ang II) type 1 (AT1) receptor, a seven -transmembrane G protein -coupled receptor, is critically involved in the development of various cardiovascular diseases. Inherently, AT1 receptor is structurally unstable, and shows spontaneous constitutive activity in an Ang II-independent manner. The constitutive activity of AT1 receptor under basal conditions contributes to the cardiac remodeling even in the absence of Ang II, when AT1 receptor is up-regulated in the heart. Furthermore, mechanical stress can activate AT1 receptor by inducing conformational switch without the involvement of Ang II, and induce cardiac hypertrophy in vivo. These agonist-independent activities of AT1 receptor can be inhibited by inverse agonists, but not by neutral antagonists. Therefore, inverse agonism of AT1 receptor blockers provides therapeutic benefits in the prevention of cardiac remodeling, and thus has potential impact on long-term outcomes in patients with cardiovascular diseases.