With the advances in mouse molecular genetics and physiology during the last decade, the mouse has become the animal model of choice for studying the genetic basis of many diseases. Terms such as "transgenic" and "knockout" have become part of a colloquial language used in most research laboratories that are investigating human diseases. These terms refer to the two most commonly used methods for analyzing the function of a gene in vivo: overexpression (transgenic mouse) and deletion (knockout mouse). Both methods have proved to be extremely useful in establishing the importance of specific genes in genetic disorders, such as hypertension. The choice of genes being investigated in relationship to hypertension was governed by the knowledge of systems regulating vascular and renal physiology. Thus, it is not surprising that most of the focus was given to the renin-angiotensin system (RAS). Apart from the RAS, other systems known to regulate vascular tone and/or electrolyte and fluid homeostasis have also been analyzed using transgenic and knockout approaches. This review briefly summarizes some of the mouse models relevant to renal mechanisms of hypertension and then discusses the future of genetic manipulation in mice for studying the genetics of hypertension.