In the past, microorganisms were not considered to be particularly important in brain development and functioning. However, recent evidence shows the existence of a bidirectional, and possibly multidimensional relationship between the body microbiota and the brain. The microbiota influence brain behavior in health or disease, by utilizing endocrine, neurocrine and immunologic signaling pathways. Also, the chemical mediators involved range from known neurotransmitters to small peptide molecules. Here, we discuss the evidence that currently exists in experimental animals and/or humans in support of the existence of a relationship involving the skin/gut microbiome, the brain, and behavior; and the mechanisms involved in such interactions. The implications of such interactions for shifts in behaviors, and the pathogenesis of behavioral and neurodegenerative disorders are also discussed. Finally, the possible clinical applications of deliberate manipulations of the microbiota composition and density for the management or prevention of behavioral and neurodegenerative disorders is discussed.