Mitochondrial oxidative damage and dysfunction contributes to a number of cell pathologies. To investigate how this damage affects cell function we have developed mitochondrially targeted antioxidants and thiol reagents by covalently linking them to lipophilic cations. The cation drives the selective accumulation of these reagents into mitochondria within cells where the antioxidants decrease oxidative damage and the thiol reagents enable measurement of the redox status of thiol proteins. In conjunction with cell and animal models of apoptosis, oxidative damage, and nitric oxide signaling, these molecules may provide new insights into the roles of mitochondria in human pathologies.