Accumulating data highlight the contribution of brain mitochondria and bioenergetics to psychiatric disorders and stress-related pathologies. Although anxiety has not received much attention in this booming literature, a bidirectional interplay between anxiety and brain mitochondria and metabolism has recently started to emerge. Substantial observations indicate alterations in mitochondria and metabolism in highly anxious individuals and, conversely, anxiety symptoms in humans suffering from mitochondrial disorders. Genetic and pharmacological efforts have made substantial progress at advancing the causal involvement of specific mitochondrial and metabolic factors in anxiety. In this review, we discuss this converging evidence and highlight the relevance of developing a research focused on targeting mitochondria as an approach to alleviate anxiety.