Antioxidants were long predicted to have lifespan-promoting effects, but in general this prediction has not been well supported. While some antioxidants do seem to have a clear effect on longevity, this may not be primarily as a result of their role in the removal of reactive oxygen species, but rather mediated by other mechanisms such as the modulation of intracellular signaling. In this review we discuss peroxiredoxins, a class of proteinaceous antioxidants with redox signaling and chaperone functions, and their involvement in regulating longevity and stress resistance. Peroxiredoxins have a clear role in the regulation of lifespan and survival of many model organisms, including the mouse, Caenorhabditis elegans and Drosophila melanogaster. Recent research on peroxiredoxins - in these models and beyond - has revealed surprising new insights regarding the interplay between peroxiredoxins and longevity signaling, which will be discussed here in detail. As redox signaling is emerging as a potentially important player in the regulation of longevity and aging, increased knowledge of these fascinating antioxidants and their mode(s) of action is paramount.