Hyperlipidemia and hypertension are frequently observed in patients with coronary artery disease. It has been proposed that an interaction between low-density lipoprotein, especially its oxidized form (ox-LDL), and renin-angiotensin system (RAS) activation is a major determinant of atherogenesis. Ox-LDL accumulation in the blood vessels enhances the expression and activation of RAS components; on the other hand, activation of RAS stimulates the accumulation of LDL and its oxidation into ox-LDL in the blood vessels. Individually ox-LDL and RAS activation induce oxidative stress and inflammatory cascade, whereas their combination exerts a synergistic effect. This concept of cross-talk between ox-LDL/hyperlipidemia and RAS activation has been proven in laboratory animals. Clinical trials also suggest that blockade of hyperlipidemia and RAS may have a synergistic salutary effect on the outcome of patients with hypertension and/or manifestations of atherosclerosis. This concept needs to be evaluated further in large clinical studies.