Autoimmune encephalitis (AE) covers a group of neurological diseases caused by autoantibodies. AE is severe but treatable. It has attracted more and more attention currently. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common AE characterized by specific autoantibody mainly against NMDAR subunit 1. Cell-based assays (CBA) on human embryonic kidney 293 (HEK293) cells and immunohistochemistry (IHC) on rat brain tissue have been widely used to detect antibody in patients with AE. However, few studies focused on the overview of these assays detecting autoantibodies in AE. Here we reviewed the detection assays in AE and compared the sensitivity and specificity of CBA and IHC. It's found that IHC got a higher positive rate than CBA in both serum and cerebrospinal fluid (CSF) when screening potential AE, while CBA was more specific. Besides, more positive samples were found in CSF than in serum by either IHC or CBA. Hence, both serum and CSF should be sent to detect antibodies by two assays to avoid misdiagnosis. CSF antibody titers were believed more clinically relevant. When positive results were shown in IHC but negative in CBA, other kinds of antibodies associated AE instead of anti-NMDAR encephalitis should be taken into account. Further studies should pay attention to serum testing for diagnosis or assessment of the disease, as CSF testing is invasive and not always available.2023 Annals of Translational Medicine. All rights reserved.