Meningitis and encephalitis are potentially life-threatening diseases with a wide array of infectious, postinfectious, and noninfectious causes. Diagnostic testing is central to determining the underlying etiology, treatment, and prognosis, but many patients remain undiagnosed due to suboptimal testing and lack of tests for all pathogens. In this article, we summarize the epidemiology, barriers to diagnosis, and current best tests for meningitis and encephalitis in developed countries. We end with a brief discussion of new test methods, such as multiplex panel-based tests and metagenomic sequencing, which are likely to alter diagnostic strategies for these conditions in the near future.