Borna disease virus (BDV) causes central nervous system (CNS) disease that is frequently manifested by behavioral abnormalities. BDV is a nonsegmented, negative, single-stranded RNA virus. On the basis of its unique genetic and biologic features, BDV is the prototypic member of a new virus family, Bornaviridae, within the order Mononegavirales. Therefore, the investigation of the molecular and cell biology of BDV may provide new insights about virus-cell interactions in the CNS. BDV is an important model system for the investigation of viral persistence in the CNS. Serologic and molecular epidemiologic studies suggest that BDV can infect humans. Despite controversy about potential association with human neuropsychiatric illnesses, BDV affords an intriguing model for the study of these illnesses. Neonatal BDV-infected rats display neurodevelopmental, physiologic, and neurobehavioral abnormalities that closely parallel some of the main features associated with several human mental disorders.