Abstract: The gastrointestinal track is inhabited by tens of trillions of microorganisms. The gut microbiota is involved in gut motility, nutrient absorption and synthesis of metabolites that influence homeostasis, metabolism and immune function. Given the influence gut microbiota has on health, there is a growing body of literature describing the gut microbiota’s impact on brain and behavior. The bidirectional nature of the gut-brain axis involves neurological, immunological and hormonal mechanisms that can induce perturbations in gut or brain homeostasis. Studies using different but complementary approaches, such as germ free mice, antibiotics, probiotics, gastrointestinal infection, and fecal microbiota transplant, have shown that the gut microbiota acting via the gut-brain axis contribute to the regulation of brain and behavior, impacting depression, stress and cognition. Moreover, gut microbiota disruption has been associated with neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and implicated in modulating disease severity in stroke. Traumatic brain injury (TBI) is a complex, acute neurological insult that can lead to chronic neurodegeneration. Understanding the influence of the gut-brain axis in the setting of TBI may create new avenues of therapeutic approaches for TBI survivors.