Oxidative stress is a key a therapeutic target for many neurological diseases. A strong rationale for oxidative stress in a given neurological disease should be the guiding factor for antioxidant therapy. Antioxidant drug development should account for both the beneficial and the harmful effects of reactive oxygen species. Biomarkers to monitor target engagement can guide antioxidant clinical trials for neurological diseases. There is widespread recognition that reactive oxygen species (ROS) play key roles in normal brain function and pathology in the context of neurological disease. Oxidative stress continues to be a key therapeutic target for neurological diseases. In developing antioxidant therapies for neurological disease, special attention should be given to the brain's unique vulnerability to oxidative insults and its architecture. Consideration of antioxidant therapy should be guided by a strong rationale for oxidative stress in a given neurological disease. This review pr