Autoreactive B cells and antibodies can be detected in a variety of neurological diseases. Their causative role has been established in some disorders and they are obviously involved in the pathogenesis of others. Some mechanisms engendering B-cell autoimmunity in animal models have been shown to operate in humans. Factors that determine B-cell immune-response patterns and the effector pathways have been identified. B-cell responses to CNS-restricted autoantigens are governed by distinctive immune reactions. Evidence has accumulated that the CNS is a permissive and, under inflammatory conditions, even a B-cell-supporting micro-environment. Data from human and animal experiments have enhanced our understanding of B-cell physiology in health and neurological disease, which has relevant diagnostic and therapeutic implications.