The first description of an autoimmune encephalitis dates back to 1888, when Hermann Oppenheim described a patient with neurological symptoms but no underlying brain pathology. The field of autoimmune encephalitides associated with antibodies targeting cell-surface antigens is rapidly expanding and new antibodies are discovered frequently. Autoimmune encephalitis is a difficult clinical diagnosis due to the similarities in the clinical, imaging and laboratory findings of many forms of autoimmune and infectious encephalitis. Treatment for suspected autoimmune encephalitis is often given empirically prior to specific antibody test results. This may include steroids and/or IVIG. The proper diagnosis and management of autoimmune encephalitis requires an organized approach. Evaluation should begin with a detailed history and physical examination to detect clues to specific causes. A diverse range of infections should be considered, and appropriate testing should be done to exclude relevant pathogens.