Calcium channel blockers (CCB) are widely used for the treatment of hypertension and angina pectoris. In vitro experiments show that CCBs decrease oxidative stress via multiple pathways. In various animal models, protective effects of CCBs against oxidative stress and organ injury have been examined. The data obtained indicate that organ-protective effects of CCBs, which cannot be simply explained by their hypotensive action, are largely mediated through their strong antioxidative effects. Clinical studies also support the idea that CCBs may be effective in reducing organ injury associated with oxidative stress during the development of hypertension. In this review, we discuss the potential mechanisms mediating the CCB-dependent antioxidative effects.