Mitochondria are cellular organelles that perform pivotal functions essential for ATP production, homeostasis, and metabolism. Moreover, mitochondria are integral to a variety of cell death and survival pathways. These roles identify mitochondria as a potential target for drugs to treat metabolic and hyperproliferative diseases. Differences in the redox state of pathogenic versus non-pathogenic cells may be exploited to achieve selective anti-proliferative and cytotoxic activity against target cell populations. Pro-oxidant drugs, such as Trisenox and Elesclomol, are demonstrating clinical utility in the treatment of cancer. Results obtained with Bz-423 in mice demonstrate the potential for mitochondria-targeted drugs to control disorders of immune function. Research associating an elevated oxidant state with mitochondrial damage, degenerative disease, and aging dictates the need for a better understanding of when and how pharmacological manipulation of mitochondrial function provides most therapeutic benefit.