As neuroscientists, psychologists, and psychiatrists are starting to appreciate the importance of the gut microbiota to mental health, it is critical to determine the mechanisms of microbiota to brain communication and thereby provide a better understanding of the aspects that may be modifiable with proper intervention in individuals with mental illness. Microbiota–brain communication is emerging as an important factor in brain development and function. Further, immune dysfunction is clearly established to play a role in mental illness. Investigators in the field have established expertise in studying the microbiota, the immune system, brain, and behavior and are poised to contribute significant novel findings to our understanding of microbiota–immune–brain communication in mental illness. This chapter provides a review of the literature related to the influence of microbiota–immune–brain communication to behavior. This research has a clear translational relevance for mental health, contributing to extant findings that indicate a role for the microbiome in brain development and behavior.