Following an introduction on the physiological and pathophysiological role of reactive oxygen species (ROS) in the heart, we will analyze the causal role of oxidative stress in heart failure from the angle of gene transfer studies of the three primary antioxidant enzymes (superoxide dismutase (SOD), catalase, and glutathione peroxidase), of thioredoxin, and of heme oxygenase-1. Here, CAT is linked to heart failure.