Mitochondria play a pivotal role in the life and death of cells and likely contribute importantly to the initiation or progression of many neurodegenerative disorders. Brain is especially vulnerable to lipid peroxidation because of its enrichment in polyunsaturated fatty acids relative to other organs. Multiple studies demonstrate the elevation of numerous lipid peroxidation products and ensuing lipid-derived carbonyls in Alzheimer's disease. In this review, we examine the data describing the effects of lipid-derived carbonyls such as 4-hydroxy-trans-2-nonenal (HNE) and acrolein upon the function of brain mitochondria as well as review the detoxification routes of these carbonyls. From these data, we show that the physical-chemical properties of these carbonyls influence their effects on mitochondria and that multiple essential mitochondrial functions are altered by these endogenous reactive carbonyls. Lastly, we examine the role of mitochondrial aldehyde detoxification pathways and their potential role in the development of AD.