The realization that the microbiota-gut-brain axis plays a critical role in health and disease has emerged over the past decade. The brain-gut axis is a bidirectional communication system between the central nervous system (CNS) and the gastrointestinal tract. Regulation of the microbiota-brain-gut axis is essential for maintaining homeostasis, including that of the CNS. The routes of this communication are not fully elucidated but include neural, humoral, immune, and metabolic pathways. A number of approaches have been used to interrogate this axis including the use of germ-free animals, probiotic agents, antibiotics, or animals exposed to pathogenic bacterial infections. Together, it is clear that the gut microbiota can be a key regulator of mood, cognition, pain, and obesity. Understanding microbiota-brain interactions is an exciting area of research which may contribute new insights into individual variations in cognition, personality, mood, sleep, and eating behavior, and how they contribute to a range of neuropsychiatric diseases ranging from affective disorders to autism and schizophrenia. Finally, the concept of psychobiotics, bacterial-based interventions with mental health benefit, is also emerging.