Neurodegeneration is a growing public health concern because of the rapid increase in median and maximum life expectancy in the developed world. Mitochondrial dysfunction seems to play a critical role in neurodegeneration, likely owing to the high energy demand of the central nervous system and its sole reliance on oxidative metabolism for energy production. Loss of mitochondrial function has been clearly demonstrated in several neuropathologies, most notably those associated with age, like Alzheimer's, Parkinson's and Huntington's diseases. Among the common features observed in such conditions is the accumulation of oxidative DNA damage, in particular in the mitochondrial DNA, suggesting that mitochondrial DNA instability may play a causative role in the development of these diseases. In this review we examine the evidence for the accumulation of oxidative DNA damage in mitochondria, and its relationship with loss of mitochondrial function and cell death in neural tissues. Oxidative DNA damage is repaired mainly by the base excision repair pathway. Thus, we review the molecular events and enzymes involved in base excision repair in mitochondria, and explore the possible role of alterations in mitochondrial base excision repair activities in premature aging and age-associated neurodegenerative diseases.