It was proved in the 1980s that human herpesvirus-6 and human parvovirus B19 cause diseases in humans. Human herpesvirus-6, a newly recognized herpesvirus, is a causative agent of exanthem subitum. The virus produces broad clinical features; complications, including fatal outcome, are frequently activated in immuno-suppressed conditions such as organ transplantation. Parvovirus B19, a small-DNA virus, infects erythroid progenitor cells. Systemic infection with parvovirus B19 is responsible for several clinical entities, such as erythema infectiosum, arthropathy, aplastic crisis, fetal death, and other disease conditions, including those in immunosuppressed hosts. Reliable diagnostic technologies and carefully designed clinical, immunologic, and virologic studies will fully delineate the clinical significance of both viral infections.