Herpesviruses 6, 7, and 8 are the most recently described members of the human herpesvirus family. Like other herpesviruses, they have the ability to establish a latent or persistent infection following primary infection, and reactivation may occur in healthy and immunocompromised people in response to different stimuli. A variety of methods are available or under development for the laboratory diagnosis of each virus, including viral isolation in cell culture, demonstration of viral antigens or nucleic acids in body fluids or tissues, and serology for detection of virus-specific antibodies. This chapter focuses on the immunologic and molecular diagnosis and monitoring of infections with human herpesvirus 6 (HHV-6), HHV-7, and HHV-8, and provides information on the unique features of the epidemiology and biological and clinical characteristics of these viruses.