HHV-6 is an opportunistic viral pathogen that has been demonstrated as the cause of often life-threatening illness in pediatric patients and transplant recipients. A substantial body of scientific evidence links HHV-6 to the etiology of such chronic diseases as multiple sclerosis. For these reasons, it is important that patients in these groups be screened for possible infection with HHV-6. Serological studies for IgG and/or IgM can be misleading, as are PCR analyses, which cannot distinguish between latent and actively replicating virus. Currently, the only reliable method for diagnosing an active infection with HHV-6 is viral isolation.