Mitochondria play a central role in the aging process. Studies in model organisms have started to integrate mitochondrial effects on aging with the maintenance of protein homeostasis. These findings center on the mitochondrial unfolded protein response (UPR(mt)), which has been implicated in lifespan extension in worms, flies, and mice, suggesting a conserved role in the long-term maintenance of cellular homeostasis. Here, we review current knowledge of the UPR(mt) and discuss its integration with cellular pathways known to regulate lifespan. We highlight how insight into the UPR(mt) is revolutionizing our understanding of mitochondrial lifespan extension and of the aging process.