The genetically programmed form of neuronal death known as apoptosis plays a role in many neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS) and Huntington's disease. Apoptosis is also responsible for neuronal death after traumatic brain and spinal cord injury, stroke, and seizures. The cognitive and behavioral consequences of all of these disorders can be devastating. Unfortunately the mechanisms that regulate neuronal apoptosis are complex. However, it is this very complexity that provides us with a wide array of potential targets for the development of anti-apoptotic strategies. Thus, our lab is currently exploring the molecular and cellular mechanisms responsible for neuronal apoptosis, with a particular focus on the role of the metals copper, zinc, and iron. Each of these metals is essential for normal central nervous system (CNS) development and function. However, imbalances, either excess or deficiency, can result in neuronal apoptosis. In this review, we show the relationship between these metals in neurodegenerative disorders and CNS injury, and the mechanisms that govern neuronal survival and apoptosis.