The field of neuronal surface-directed antibody-mediated diseases of the central nervous system has dramatically expanded in the last few years and now forms an important cluster of treatable neurological conditions. In this review, we focus on three areas. First, we review the demographics, clinical features and treatment responses of these conditions. Second, we consider their pathophysiology and compare autoantibody mechanisms and their effects to genetic or pharmacological disruptions of the target antigens. Third, we discuss areas of controversy within the field, propose possible resolutions, and explore new directions for neuronal surface antibody-mediated diseases.