The cumulative evidence from preclinical and clinical studies supports the role for the gut microbiome in host physiology, brain function, and behavior. This opens up the possibility of therapeutic targeting of host–microbe interactions in central nervous system (CNS) disorders. Many of these microbial options fall under the umbrella of psychobiotics, a term that incorporates a range of interventions that affect microbiota–gut–brain axis signaling, including probiotics, prebiotics, synbiotics, postbiotics, fermented food, and fecal microbiota transplantation. There are an expanding range of therapeutic targets along various signaling pathways of the microbiome–gut–brain axis that can be recruited for the management of symptoms in CNS and gastrointestinal disorders. Further work is required to gain a more detailed understanding of the mechanisms involved in the action of psychobiotics as we move toward clinical translation. This will inform guidelines and strategies for the clinical deployment of psychobiotics, either as adjunctive therapies or direct options.