 The human brain consumes 20% of the total basal oxygen, O2, budget to support ATP-intensive neuronal activity. Without sufficient O2 to support ATP demands, neuronal activity fails, leading to neurodegeneration. This is due to the brain being susceptible to oxidative stress, which can be caused by various factors including unsaturated lipids, mitochondria, calcium, glutamate, modest antioxidant defense, redox active transition metals, and neurotransmitter auto oxidation. Additionally, RNA oxidation has been found to be an underappreciated cause of oxidative stress. The complex interplay between these factors determines neuronal susceptibility to oxidative stress in a dynamic context and neural identity-dependent manner. This article was authored by James Nathan Kobaly, Maria Luisa Fiorello, and Damian Miles Bailey.