Diagnosing autoimmune encephalitis (AE) is complicated by several factors, including issues with availability, sensitivity, and specificity of antibody testing, particularly with variability in assay techniques and new antibodies being rapidly identified; nonspecific findings on MRI, EEG, and lumbar puncture; and competing differential diagnoses. Through case-based discussions with 3 experts from 3 continents, this article discusses the challenges of AE diagnosis, important clinical characteristics of AE, preferences for methods of autoantibody testing and interpretation, and treatment-related questions. In particular, we explore the following question: If a patient's clinical presentation seems consistent with AE but antibody testing is negative, can one still diagnose the patient with AE? Furthermore, what factors does one consider when making this determination, and should treatment proceed independent of antibody testing in suspected cases? The same case-based questions were posed to the rest of our readership in an online survey, the results of which are also presented.