The role of mitochondria in aging and disease remains contentious more than 40 years after the mitochondrial free radical theory of aging was first proposed. As part of a wider cross-journal series on contemporary mitochondrial biology, Longevity & Healthspan presents a thematic series of four reviews that discuss the evidence for and against the modern incarnations of the theory, and examine the relevance of mitochondrial membrane phospholipid unsaturation and the interactions of mitochondria with sex hormones.