Depression and anxiety are common psychological disorders that place a high burden on individuals and society. The current pharmacological and nonpharmacological treatment of mood disorders remains suboptimal, leading many to look toward microbiota-based interventions as a new potential treatment paradigm. The physiological and preclinical rationale for a microbiota-based intervention is strong, as it is clear now that our brain and gut microbiota develop in parallel and remain in communication via the brain-gut-microbiota axis throughout our lifespan. It is also clear that changes in the homeostasis between the gut and its resident microbiota can lead to behavioral changes in animals and brain changes in humans, potentially driving the symptoms of anxiety and depression. This chapter will provide an overview of the brain-gut-microbiota axis and its relevance to mood disorders and their treatment.