With advances in genetic manipulation and molecular biological and physiological techniques, the mouse has become the animal model of choice for studying the genetic basis of human diseases. The two most commonly used methods for analyzing the function of a gene in vivo, overexpression (transgenic mouse) and deletion (knockout mouse), have been extremely useful in establishing the importance of genes in genetic disorders. The renin-angiotensin system (RAS) is one of the most widely studied systems controlling blood pressure. Although the primary site of Ang-II production is the plasma, all the components of the RAS cascade are expressed in many tissues, including the brain. This review briefly summarizes systemic and tissue-specific transgenic and knockout mouse models of the RAS for determining the role of this system in the regulation of blood pressure and in the pathogenesis of hypertension, with a focus on the RAS in the brain.