Reactive oxygen species (ROS) are elevated in humans with hypertension many of which develop end-stage renal disease (ESRD), and antioxidant capacity is decreased. About one-half of essential hypertensives have a salt-sensitive type of hypertension, and the amount of renal damage that occurs in salt-sensitive hypertensives greatly exceeds that of non-salt-sensitive hypertensives. Antioxidant therapy can improve cardiovascular outcomes in humans but only if sufficient doses are used. Salt-sensitive hypertensive animal models, especially Dahl salt-sensitive rats, have been used to investigate the relationship between hypertension, ROS and end-stage renal damage. In experimental salt-sensitive hypertension, ROS increase and significant renal damage occur. In the Dahl salt-sensitive (S) rat on high Na for 3 weeks, renal damage is mild, renal levels of superoxide dismutase are decreased, and treatment with Tempol reduces arterial pressure. In the Dahl S rat on high Na for 5 weeks, renal damage is severe, GFR and renal plasma flow are decreased, and renal superoxide production is high. Treatment with vitamins C and E decreases renal superoxide production and renal damage and prevents the decrease in renal hemodynamics. Antioxidant treatment reduces arterial pressure, aortic superoxide production and renal inflammation in DOCA-salt rats, and decreases blood pressure and aortic superoxide release and increases bioactive nitric oxide in SHR stroke-prone rats. In conclusion, in both human and experimental salt-sensitive hypertension, superoxide production and renal damage are increased, antioxidant capacity is decreased, and antioxidant therapy can be helpful.