Oxidative stress is a ubiquitous phenomena in all cell types, and it is primarily produced in mitochondria which are essential for multicellular life. Oxidative stress targets can be wide ranging and include nucleic acids and a variety of macromolecules. This review discusses the role of oxidative stress in the context of animal models, focusing in particular on animal models of aging, as well as the development of a new class of therapeutic small molecular weight antioxidants that have proven effective in extending the lifespan of a simple invertebrate nematode.