Mitochondrial Free Radical Theory of Aging not adequate to explain effects of age and reversal of dysfunction. The focus on oxidative damage and free radical scavenging in the analysis of the Mitochondria Free Radical Theory of Aging (MFRTA) is not adequate to test the role of oxidative stress in aging. Our recent papers demonstrate a dynamic interaction between oxidants and mitochondrial energetics that 1) are dependent on the interaction between the mitochondria and cell environment, and 2) cannot be explained by the traditional view of oxidative damage. Cellular oxidants play an important role in cell signaling through their interaction with the redox buffering system and modification of protein thiol groups. This system, comprising the metabolites, GSH and NADPH and enzymes such as thioredoxins, peroxiredoxins, and glutaredoxins among others, exists in both the mitochondria and cytosolic compartments and is responsible for sensing and responding to changes in the redox status of the cell. Communication between the redox buffering systems and cellular physiology primarily occurs through reversible post-translational modifications of protein thiols, including S-glutathionylation (PSSG), sulfenylation, and S-nitrosylation. One area of focus of our research is attempting to understand the interaction mitochondrial function, redox biology, and the thiol proteome in health and disease.