Reactive oxygen species (ROS) are important mediators of myocardial remodeling. However, the precise molecular mechanisms by which ROS exert their effects are incompletely understood. ROS induce oxidative posttranslational protein modifications that can regulate the function of structural, functional, and signaling proteins. For example, oxidative modification of free reactive thiols (S-thiolation) on the small G protein Ras increases Ras activity and thereby promotes ROS-dependent hypertrophic signaling in cardiac myocytes. By reducing thiols and restoring reversible thiol modifications, thioredoxin and glutaredoxin can act as regulators of ROS-mediated protein function. Understanding the regulation and functional relevance of oxidative protein modifications in myocardial remodeling may lead to new therapeutic strategies.