Mitochondria are the cellular powerhouses, fuelling metabolic processes through their generation of ATP. However we now recognise that these organelles also have pivotal roles in the generation of reactive oxygen species (ROS) and the regulation of cell death, inflammation and metabolism. Mitochondrial dysfunction therefore leads to oxidative stress, cell death, inflammation and altered metabolism, which are all key processes in atherosclerosis. Recent evidence indicates that mitochondrial DNA (mtDNA) damage is present and promotes atherosclerosis through mitochondrial dysfunction. In this review we discuss the role and mechanisms linking mtDNA damage and atherosclerosis, and identify areas of mitochondrial biology that may yield potential therapeutic targets.