Increasing evidence suggests that a subset of gastrointestinal motility disorders is associated with the presence of circulating antibodies. These antibodies are directed against various molecular targets, the best known being anti-neuronal nuclear antibody (ANNA-1 or anti-Hu) associated with paraneoplastic motility disorders. There is also evidence that the presence of distinct autoantibody profiles is associated with non-paraneoplastic motility disorders. This review focuses on the types of antibodies associated with gastrointestinal motility disorders and the significance of these antibodies. Algorithms are suggested for the work-up and treatment of patients with circulating antibodies associated with gastrointestinal motility disorders.