The early detection and specific diagnosis of viral infections of the central nervous system are important because many of these diseases are potentially treatable. However, clinical symptoms and physical examination are often nonspecific, and rapid diagnostic tests are available for some, but not all, viruses. Neuroimaging, in conjunction with clinical history and laboratory tests, plays an important role in narrowing the differential diagnoses. In this article, we review the clinical features, imaging characteristics, diagnosis, and treatment of the more common viral infections and prions that involve the central nervous system.