Superoxide dismutase (SOD) is a group of enzymes, which is often regarded as the first line of cellular defense against the deleterious effects of reactive oxygen species (ROS). Oxidative stress that results from the production and reactivity of ROS has emerged as a main pathogenic event in human diseases, including neurodegenerative conditions such as Parkinson’s disease (PD). In this chapter we summarize the large body of information on the brain’s distribution of SOD with special attention to those areas affected in PD, and we discuss the potential significance of SOD in the pathogenesis of PD. Evidence from cellular and animal models of PD supports the hypothesis that SOD plays a critical role in the neurodegenerative process of PD, and implies that SOD-based neuroprotective therapies should be considered for the treatment of this illness.