The worldwide epidemic of obesity has become an important public health issue, with serious psychological and social consequences. Obesity is a multifactorial disorder in which various elements (genetic, host, and environment), play a definite role, even if none of them satisfactorily explains its etiology. A number of neurological comorbidities, such as anxiety and depression, charges the global obesity burden, and evidence suggests the hypothesis that the brain could be the seat of the initial malfunction leading to obesity. The gut microbiome plays an important role in energy homeostasis regulating energy harvesting, fat deposition, as well as feeding behavior and appetite. Dietary patterns, like the Western diet, are known to be a major cause of the obesity epidemic, probably promoting a dysbiotic drift in the gut microbiota. Moreover, the existence of a “gut–brain axis” suggests a role for microbiome on hosts’ behavior according to different modalities, including interaction through the nervous system, and mutual crosstalk with the immune and the endocrine systems. In the perspective of obesity as a real neuropsychological disease and in light of the discussed considerations, this review focuses on the microbiome role as an emerging director in the development of obesity.