Human herpesvirus-6 (HHV-6) and -7 (HHV-7) infections typically are silent or manifested as mild febrile illnesses including classic roseola. In addition, case reports and epidemiologic data support the rare occurrence of HHV-6 encephalitis in immunocompromised as well as immunocompetent subjects. Although many other diseases have been putatively associated with HHV-6 or HHV-7, these associations are not well documented due to small numbers, use of tests incapable of distinguishing latent from replicating virus, potential virus cross-reactivity, or contradictory results. Further careful studies are needed to confirm these disease associations. Laboratory tests for diagnosing active HHV-6 and HHV-7 infections include virus culture, antigen detection, and polymerase chain reaction of cell-free biologic fluid. Although HHV-6 and HHV-7 are inhibited by several antiviral drugs in the laboratory, including ganciclovir and foscarnet, no clinical trials have assessed their benefit. Nevertheless, treatment may be considered for patients with serious HHV-6- or HHV-7-associated disease confirmed with accurate virologic tests.