Borna disease virus (BDV) causes central nervous sytem (CNS) disease in several vertebrate species characterized by behavioral abnormalities. Based on its unique features, BDV represents the prototype of a new virus family. BDV provides an interesting model for the investigation of the mechanisms and consequences of viral persistence in the CNS. BDV persistence has been associated with immune-mediated damage, neurodevelopmental abnormalities, as well as alterations in cell differentiated functions that affect brain homeostasis. Moreover, seroepidemiological data and recent molecular studies indicate that BDV can infect humans and is associated with certain neuropsychiatric diseases. The potential role of BDV in human mental health provides additional impetus for the investigation of this novel neurotropic infectious agent.