Introduction: The incidence and prevalence of neurodegenerative diseases increase with life expectancy. Brain, for physiological and biochemical reasons, has a high sensitivity to oxidative stress. Therefore, maintaining the redox homeostasis is essential for brain cells. In addition, brain antioxidant levels are limited compared to other tissues. In this article, different mechanisms involved in the production of endogenous and exogenous reactive oxygen species and the role of oxidative stress in neurodegenerative diseases were discussed. Redox imbalance occurs when antioxidant capacity doesn't overcome free radicals, which can lead to tissue damage, cell death or disease onset. This article also reviews various molecular and signaling mechanisms involved in oxidative stress management in neurodegenerative diseases. Conclusion: Although the induction and role of oxidative stress in neurodegenerative disease have been approved, its role in pathogenesis of some of the neurodegenerative diseases needs to be further investigated. It is possible that with antioxidant therapy, we could modulate oxidative status and prevent or treat these diseases.