Mitochondria are key organelles with a critical role as the main source of energy supply. Mitochondrial dysfunction can lead to several disorders, including neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases and the aging process. The mitochondrial respiratory chain is the main source of reactive oxygen species and because it is located in the inner mitochondrial membrane, it is also susceptible to oxidative damage, as well as other biomolecules in the vicinity, such as mitochondrial DNA. Nitric oxide is also found in the mitochondrial matrix and is involved in physiological pathways such as induction of apoptosis and generation of nitrosative stress. In this review we will discuss the complex mechanisms involved in the relationship between mitochondrial dysfunction, oxidative stress and neuronal death.