The article discusses the selective neuronal vulnerability (SNV) to oxidative stress (OS) in the brain, which is a critical factor in brain aging and neurodegenerative diseases. OS is caused by an imbalance between the production and detoxification of reactive oxygen and nitrogen species (ROS/RNS). While many brain neurons can cope with increased OS, certain populations of neurons are particularly vulnerable, often exhibiting functional decline and cell death during normal aging or in neurodegenerative conditions like Alzheimer's disease (AD) and Parkinson's disease (PD). The review highlights several molecular and cellular factors contributing to SNV, including high intrinsic OS, high demand for ROS/RNS-based signaling, low ATP production, mitochondrial dysfunction, and high inflammatory response. Additionally, other factors such as deficient DNA damage repair, low calcium-buffering capacity, and glutamate excitotoxicity are discussed. The study of SNV to OS provides insights into how specific forms of cell stress cause selective neuronal losses and may lead to the development of interventions to protect vulnerable neurons.The article discusses the selective neuronal vulnerability (SNV) to oxidative stress (OS) in the brain, which is a critical factor in brain aging and neurodegenerative diseases. OS is caused by an imbalance between the production and detoxification of reactive oxygen and nitrogen species (ROS/RNS). While many brain neurons can cope with increased OS, certain populations of neurons are particularly vulnerable, often exhibiting functional decline and cell death during normal aging or in neurodegenerative conditions like Alzheimer's disease (AD) and Parkinson's disease (PD). The review highlights several molecular and cellular factors contributing to SNV, including high intrinsic OS, high demand for ROS/RNS-based signaling, low ATP production, mitochondrial dysfunction, and high inflammatory response. Additionally, other factors such as deficient DNA damage repair, low calcium-buffering capacity, and glutamate excitotoxicity are discussed. The study of SNV to OS provides insights into how specific forms of cell stress cause selective neuronal losses and may lead to the development of interventions to protect vulnerable neurons.