More than 50 million Americans display blood pressures outside the safe physiological range. Unfortunately for most individuals, the molecular basis of hypertension is unknown, in part because pathological elevations of blood pressure are the result of abnormal expression of multiple genes. This review identifies a number of important blood pressure regulatory genes including their loci in the human, mouse, and rat genome. Phenotypes of gene deletions and overexpression in mice are summarized. More detailed discussion of selected gene products follows, beginning with proteins involved in ion transport, specifically the epithelial sodium channel and sodium proton exchangers. Next, proteins involved in vasodilation/natriuresis are discussed with emphasis on natriuretic peptides, guanylin/uroguanylin, and nitric oxide. The renin angiotensin aldosterone system has an important role antagonizing the vasodilatory cyclic GMP system.