Trillions of microbes cover the surfaces of our bodies and inhabit our gastrointestinal tract—the importance of these microbes to mental health has moved to the forefront of neuroscience and psychiatry. Based on a foundation of research derived from animal studies that demonstrated the vital role for microbiota–brain communication in brain development, behavior, and brain function over the life span, clinical studies have started to consider the microbiome in psychiatric disorders. Alterations in microbiota diversity and composition have been reported in autism spectrum disorder, major depression, bipolar depression, anxiety disorders, schizophrenia, and psychotic disorders. Understanding the basis of these differences and their functional impact, mapping them to clinical symptoms, severity, and host biology is the next step in this fast-moving area of research. Moreover, the opportunity to harness our knowledge of the microbiome to develop novel therapies and to improve outcomes in psychiatry warrants greater attention.