The identification of the mitochondrion as the gatekeeper of the life and death of a cell and the appreciation of the role of mitochondrial dysfunction in a range of clinical disease processes have made the mitochondrion a target for drug delivery. Accordingly, strategies are being developed for the targeted delivery of antioxidants to mitochondria. Recent studies show that triphenylphosphonium-based antioxidants and amino acid- and peptide-based antioxidants protect mitochondria against oxidative insult. Future studies will undoubtedly exploit the unique biophysical and biochemical properties of mitochondria, including mitochondrial activation of prodrugs, for the targeted delivery of cytoprotective agents.