Primary human herpesvirus 6 (HHV-6) infection causes exanthem subitum,a common febrile illness,in infants. At the time of primary infection with HHV-6, the virus rarely causes encephalitis. Recently, various types of clinical features of patients with HHV-6 encephalitis have been reported. Therefore, appropriate procedures for the management of these patients should be established on the basis of the clinical features of the patients. In addition to primary infection with the virus, reactivation of HHV-6 can be associated with encephalitis in the case of immunocompromised patients. Numerous copies of the viral DNA were detected in the cerebrospinal fluid collected from the patients. This finding suggests that active viral replication possibly occurred in the brain tissues of these patients. A typical clinical feature of post transplant HHV-6 encephalitis, was the development of amnesia; further, abnormal magnetic resonance imaging (MRI) findings in the hippocampal regions were observed. Thus, HHV-6 is considered to be one of the causative agents for limbic encephalitis that develops in immunocompromised patients. On the basis of the results of in vitro analysis, it has been suggested that ganciclovir and foscarnet have antiviral effects against HHV-6. Although a double-blind control study has not been performed to elucidate the effectiveness of these 2 drugs in vivo, either of the 2 antiviral drugs should be used for the treatment of patients with HHV-6 encephalitis.