Autoimmunity of the peripheral and central nervous system is an important cause of disease and long-term neurological disability. Autoantibodies can target both intracellular and extracellular neuronal epitopes. Autoantibodies that target cell-surface epitopes infer pathogenicity through several distinct mechanisms, while patients often respond to immunotherapy. However, the underlying pathogenesis of these autoantibodies is yet to be fully understood. Human stem cell–based disease modeling, and the rise of induced pluripotent stem cell technology in particular, has revolutionized the fields of disease modeling and therapeutic screening for neurological disorders. These human disease models offer a unique platform in which to study autoimmunity of the nervous system. Here, we take an in-depth look at the possibilities that these models provide to study neuronal autoantibodies and their underlying pathogenesis.