Autoimmune encephalitis (AE) is a group of disorders causing synaptic receptor dysfunction with a broad range of neurological symptoms that has been historically difficult to differentiate clinically. Today, AE represents an excellent example of the rapid determination of the cause of a disease and the ability to identify potential treatments using relatively simple basic science techniques of investigation. Of the number of autoimmune encephalitides identified thus far, one of the best examples of the impact of basic science studies on disease management is NMDA receptor mediated autoimmune encephalitis (NMDAr-AE). In this review, we will provide an overview of the epidemiology of NMDAr-AE, clinical features and treatments, and the basic science tools and techniques that were used to identify the cause, correlate symptoms to underlying pathophysiology, and to understand the mechanism of disease pathology.