Recent experimental and clinical studies have suggested that oxidative stress is enhanced in heart failure. The production of oxygen radicals is increased in the failing heart whereas antioxidant enzyme activities are preserved normal. Mitochondrial electron transport is an enzymatic source of oxygen radical generation and also a target against oxidant-induced damage. Chronic increases in oxygen radical production in the mitochondria can lead to a catastrophic cycle of mitochondrial DNA damage as well as functional decline, further radical generation, and cellular injury. These cellular events might play an important role in the development and progression of myocardial remodeling and failure.