Significance Successful response to stress requires that an organism rapidly direct its energy toward an appropriate survival response. The brain is central to successful survival decisions, and therefore its ability to allocate energetic resources precisely in response to stress is paramount. Glucocorticoid stress hormones have long been known to assist in the liberation of energy during stress via their ability to regulate the activity of the nuclear genome. The cellular powerhouse, the mitochondria, also contains a genome; herein we show that glucocorticoids, acting through their receptors, regulate the expression of mitochondrial genes in the brain. These findings demonstrate a direct molecular linkage between stress and mitochondrial function.