Mitochondria are the organelles of aerobic respiration. They consume the oxygen we breathe to stay alive and generate energy for cells to function. But oxygen can be dangerous. Indeed, mitochondria generate the majority of reactive oxygen species that are prime suspects among the causes of aging. Mitochondria have been influential elements of evolving eukaryotic cells for perhaps 2 billion years, since a eubacterium fused with an archaebacterium. The picture that has emerged from this long history of genomic fusion is that of a complex network of nuclear-mitochondrial cross-talk. Here, we discuss the biochemical and genetic conflicts between mitochondria and nucleus, which have shaped the role of mitochondria in aging, and point to new paths for further investigations.