The renin-angiotensin system (RAS) is a critical regulator of blood pressure and fluid homeostasis. Components of the RAS, including renin, angiotensin-converting enzyme (ACE), and angiotensin type 1 (AT1) receptors, are expressed throughout the body in tissues that may impact blood pressure control. Blocking actions of individual components of the RAS lowers blood pressure. Although it has been suggested that control of sodium excretion by the kidney is the dominant mechanism for blood pressure regulation by the RAS, pharmacologic antagonists or conventional gene targeting experiments globally interrupt the RAS and cannot discriminate its actions in the kidney from other tissue compartments. Recent experiments using kidney cross-transplantation and genetically engineered mice have confirmed a major role for angiotensin II acting via AT1 receptors in the kidney in hypertension. These actions of renal AT1 receptors are required for the development of angiotensin II-dependent hypertension and cardiac hypertrophy. These findings, with previous experiments, clearly establish the critical role of the kidney in the pathogenesis of hypertension and its cardiovascular complications.