This review article by Sonia Gandhi and Andrey Y. Abramov from the UCL Institute of Neurology explores the role of oxidative stress in neurodegenerative diseases. The authors discuss the mechanisms by which reactive oxygen species (ROS) are produced and their impact on cellular function, particularly in the brain, which is highly vulnerable to oxidative stress due to its high oxygen demand and abundant peroxidisable substrates. They highlight the evidence of oxidative stress in Alzheimer's disease (AD) and Parkinson's disease (PD), two of the most common neurodegenerative disorders, and the potential of antioxidants as therapeutic agents. However, the authors also address the challenges in translating this hypothesis into effective clinical treatments, noting that antioxidant therapies have not shown significant benefits in large randomized controlled trials. The review delves into the sources of ROS, including mitochondrial dysfunction, NADPH oxidase, and xanthine oxidase, and discusses the mechanisms by which oxidative stress leads to selective neuronal degeneration. Despite the promising animal model results, the authors emphasize the need for further research to understand the complex interplay between oxidative stress and neurodegeneration, as well as the potential for multiple therapeutic approaches to effectively reduce oxidative stress and slow disease progression.This review article by Sonia Gandhi and Andrey Y. Abramov from the UCL Institute of Neurology explores the role of oxidative stress in neurodegenerative diseases. The authors discuss the mechanisms by which reactive oxygen species (ROS) are produced and their impact on cellular function, particularly in the brain, which is highly vulnerable to oxidative stress due to its high oxygen demand and abundant peroxidisable substrates. They highlight the evidence of oxidative stress in Alzheimer's disease (AD) and Parkinson's disease (PD), two of the most common neurodegenerative disorders, and the potential of antioxidants as therapeutic agents. However, the authors also address the challenges in translating this hypothesis into effective clinical treatments, noting that antioxidant therapies have not shown significant benefits in large randomized controlled trials. The review delves into the sources of ROS, including mitochondrial dysfunction, NADPH oxidase, and xanthine oxidase, and discusses the mechanisms by which oxidative stress leads to selective neuronal degeneration. Despite the promising animal model results, the authors emphasize the need for further research to understand the complex interplay between oxidative stress and neurodegeneration, as well as the potential for multiple therapeutic approaches to effectively reduce oxidative stress and slow disease progression.