Herpes Virus Infections have been prevalent as early as ancient Greek times. Hippocrates is known to have described the cutaneous spreading of herpes simplex lesions and scholars of Greek civilization define the greek word "herpes" to mean "to creep or crawl" in reference the spreading nature of the herpetic skin lesions. Even Shakespeare is thought to have been familiar with recurrent herpes simplex lesions and their transmission. In Romeo and Juliet, he writes Queen Mab to say "O'er ladies lips, who straight on kisses dream, which oft the angry Mab with blisters plagues, because their breaths with sweetmeats tainted are." Nonetheless, it was not until 1893 when Vidal recognized that human transmission of Herpes Simplex infection from one individual to another.

During the twentieth century, HSV research blossomed. Histopathologic studies characterized the multinucleated giant cells associated with herpesvirus infection. And in 1919, Lowenstein confirmed experimentally the infectious nature of HSV that Shakespeare had only suspected. In the 1920's and 1930's, the natural history of HSV was widely studied and it was found that HSV not only infects the skin, but also the central nervous system. In the 1930's, host immune responses to HSV were thoroughly examined and the property of HSV known as latency was characterized. By the 1940's and 1950's, research abounded on the many diseases caused by HSV. More recent research has focused on antiviral research, differences between HSV strains, and using HSV vectors for use in vaccines.

Varicella-Zoster Virus (VZV) also has a long recorded history. However, historical accounts often fail to distinguish between the poc marks caused by VZV and those caused by small pox. It was only in the late eighteenth century that Heberden established a way to clinically differentiate between the two diseases. In 1888, it was suggested by von Bokay that chickenpox and herpes zoster were due to the same causal agent. It was not until Weller and Stoddard isolated virus both from chickenpox and zoster and compared the viruses that this connection was confirmed: chickenpox and herpes zoster were indeed due to the same virus!

The history of Epstein-Barr virus is much more recent. As recently as 1964, Epstein and Barr isolated virus particles from lymphoblastoid cell lines from established from explants of Burkitt's lymphoma. The virus they isolated was named after them and became known as Epstein-Barr virus. Since then, Epstein Barr virus (EBV) has been found to be the predominant viral cause of cancer in man, playing an etiological role in Burkitt's Lymphoma, nasopharyngeal carcinoma, and B cell lymphomas. Perhaps because of the recent discovery of EBV, it is commonly implicated as the etiological agent for many cancers and diseases in which it plays no role.

Cytomegalovirus (CMV) too was only isolated recently. It was first found in patients with congenital cytomegalic inclusion disease. The recent isolation can probably be explained by the fact that it almost never is symptomatic in the immunocompetant patient. So, despite the ubiquity of CMV's worldwide distribution, so few people are symptomatic that CMV was not recognized until recently. All of the diseases associated with CMV are characterized by enlarged cells, after which the name cytomegalovirus derives.