The differential diagnosis of inflammatory myelopathies is broad. Autoimmune myelopathies represent a heterogeneous but significant portion of inflammatory myelopathies. The discovery of serologic biomarkers of autoimmune myelopathies (including aquaporin-4 and collapsin response-mediator protein-5 [CRMP-5] immunoglobulin [Ig]Gs) supports the concept of an autoimmune attack targeting the spinal cord. Neuroimaging, in particular MRI, may reveal distinctive patterns of signal abnormality suggesting an autoimmune etiology, such as longitudinally extensive transverse myelitis in neuromyelitis optica spectrum disorders or tract-specific changes in paraneoplastic disorders. IgG biomarkers of autoimmune myelopathies enable more precise disease classification and have the potential to direct a cancer search, predict outcome, guide therapeutic decision making, and lead to future development of antigen-specific targeted therapies. The goal of initial immunotherapy is to reverse or halt progression. Long-term immunotherapy aims to maintain remission and prevent relapse.