Angiotensin II, generated from its precursor angiotensinogen by renin and angiotensin-converting enzyme (ACE), mediates its biological effects via two different classes of G protein-coupled receptors, termed angiotensin II AT1 receptors and AT2 receptors. Transgenic mouse models have greatly advanced our understanding of the specific functions of the individual parts of the renin angiotensin aldosterone system (RAAS). Recently, all components of the RAAS have been deleted by homologous recombination in the mouse genome. This review summarizes the in vivo significance of the available knockout mouse lines of the RAAS. While most of the classical functions of the RAAS are mediated via AT1 receptor, recent in vivo evidence suggests that AT2 receptors may antagonize the cardiovascular effects of AT1 receptor activation. Most importantly, AT2 receptors are required to inhibit the growth-promoting effects of AT1 receptors in vascular smooth muscle cells and in cardiac myocytes. Targeted deletions of angiotensinogen and ACE genes have extended our knowledge of the embryonic functions of the renin angiotensin system. Most recently, a novel angiotensin-converting-enzyme (ACE2) has been cloned and deleted by homologous recombination in mice. Thus, the experimental findings from transgenic animal models offer new insights into the physiological regulation of the RAAS and help in the development of novel therapeutical strategies for treating human diseases.