Pharmacogenomics aims to individualize therapy based on the individual’s genetic profile. There are numerous endogenous oxidants and antioxidant proteins (Figure 1) in different organs, including the kidney, brain, and cardiovascular system, that keep a normal redox balance in the body. Genetic polymorphisms that affect the expression and activity of some of these pro-oxidant or antioxidant genes are associated with human hypertension (Table 1). These polymorphisms could influence the response to antihypertensive drugs, i.e., pharmacogenomics. This review provides an update on the genes associated with the regulation of ROS production in hypertension and discusses the controversies on the use of antioxidants in the treatment of hypertension, including the antioxidant effects of antihypertensive drugs.