The causes of the selective neurodegeneration in Parkinson disease (PD) and amyotrophic lateral sclerosis (ALS) are unknown and commonalities among these and other age-related neurodegenerative diseases continue to be sought. Morphologic, biochemical, molecular genetic, and cell/animal model studies suggest that mitochondria might be a convergence point for neurodegeneration. The functions and properties of mitochondria might render subsets of selectively vulnerable neurons intrinsically susceptible to cellular aging and stress. In PD, mutations in putative mitochondrial proteins have been identified recently and mitochondrial DNA mutations have been found in nigral neurons. In ALS, changes occur in mitochondrial respiratory chain enzymes and in mitochondrial cell death proteins, indicative of an activation of programmed cell death pathways. Mouse models are beginning to reveal possible principles governing the biology of selective neuronal vulnerability that implicate mitochondria in neuronal death processes ranging from apoptosis to necrosis. This review presents how malfunctioning mitochondria might contribute to neuronal death in PD and ALS.